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Blood, Vol. 89 No. 10 (May 15), 1997:
pp. 3636-3643
Transcription Factor GATA-2 Is Required for Proliferation/Survival of Early Hematopoietic Cells and Mast Cell Formation, But Not for Erythroid and Myeloid Terminal Differentiation
By
Fong-Ying Tsai and
Stuart H. Orkin
From the Division of Hematology/Oncology and Howard Hughes Medical Institute, Children's Hospital, Boston; and Dana Farber Cancer Institute, Department of Pediatrics, Harvard Medical School, Boston, MA.
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ABSTRACT |
The zinc-finger transcription factor GATA-2 plays a critical role in maintaining the pool of early hematopoietic cells. To define its specific functions in the proliferation, survival, and differentiation of hematopoietic cells, we analyzed the hematopoietic potential of GATA-2-/- cells in in vitro culture systems for proliferation and maintenance of uncommitted progenitors or differentiation of specific lineages. From a two-step in vitro differentiation assay of embryonic stem cells and in vitro culture of yolk sac cells, we demonstrate that GATA-2 is required for the expansion of multipotential hematopoietic progenitors and the formation of mast cells, but dispensable for the terminal differentiation of erythroid cells and macrophages. The rare GATA-2-/- multipotential progenitors that survive proliferate poorly and generate small colonies with extensive cell death, implying that GATA-2 may play a role in both the proliferation and survival of early hematopoietic cells. To explore possible mechanisms resulting in the hematopoietic defects of GATA-2-/- cells, we interbred mutant mouse strains to assess the effects of p53 loss on the behavior of GATA-2-/- hematopoietic cells. Analysis of GATA-2-/-/p53-/- compound-mutant embryos shows that the absence of p53 partially restores the number of total GATA-2-/- hematopoietic cells, and therefore suggests a potential link between GATA-2 and p53 pathways.
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INTRODUCTION |
PRODUCTION OF BLOOD cells through the life of the individual is dependent on the development and maintenance of pluripotent hematopoietic stem cells (HSCs), which are required to self-renew and yet provide sufficient numbers of multipotential progenitors and committed precursors. HSCs are thought to be quiescent and replicate only occasionally. The progenitor pool, on the other hand, is highly dynamic. In response to environmental signals, largely provided by hematopoietic cytokines, progenitor cells proliferate, die, or undergo further differentiation.1-3 Signals transmitted through cytokine receptors ultimately influence the function of nuclear transcription factors or associated factors. Accordingly, cells execute programs of gene expression and express lineage-restricted markers.4,5 Transcription factors critical to the formation or maintenance of HSCs and early hematopoietic progenitors are of particular interest in dissecting the mechanisms of lineage selection and maturation.
Three members of the GATA family of transcription factors, GATA-1, GATA-2, and GATA-3, have emerged as important transcription factors in hematopoietic cells.6,7 These proteins recognize highly similar (or identical) GATA motifs in target gene promoters or enhancers and function as transcriptional activators in conventional reporter assays. GATA-1 and GATA-3 have been studied primarily in relation to lineage-specific transcription. GATA-1, the founding member of this family, is expressed at a high level in erythroid cells, mast cells, megakaryocytes, and eosinophils, and at a low level in multipotential progenitors.8,9 Erythroid precursors lacking GATA-1 fail to differentiate beyond the proerythroblast stage either in vitro10 or in vivo.11 GATA-3, which is expressed in T lymphocytes,12,13 is essential for T-lymphoid cell development.14 The related GATA family member GATA-2 is expressed in broad distribution among hematopoietic cells, with particularly prominent expression in early progenitors, as well as megakaryocytes and mast cell lineages.15-18
To show the in vivo requirement for GATA-2 in hematopoiesis, we previously used gene-targeting in mouse embryonic stem (ES) cells and generated mouse embryos lacking GATA-2.19 GATA-2-/- mice die at approximately embryonic day 10 to 11 (E10-E11) with severe anemia. By chimeric analysis in which GATA-2-/- ES cells were introduced into wild-type blastocysts, we also observed a profound defect in the production of cells of all lineages during definitive (or adult) hematopoiesis in the absence of GATA-2. Furthermore, study of in vitro differentiation of GATA-2 null ES cells revealed significant impairment, particularly in responses to c-kit ligand [KL] or stem cell factor [SCF]. Taken together, these findings point to a critical role for GATA-2 in early hematopoietic cells, possibly influencing the proliferation or maintenance of progenitors.
In the study described here, we used in vitro differentiation of ES cells and in vitro culture of yolk sac hematopoietic cells to establish more precisely the position in the hematopoietic hierarchy at which GATA-2 is required. Our findings extend previous inferences regarding the role of GATA-2 in the proliferation and/or survival of multipotential progenitors, and also show that GATA-2 is required for generation of mast cells, but is dispensable for maturation of erythroid cells and macrophages. To examine whether p53, a key regulator of both cell-cycle arrest and apoptosis, is involved in the mechanisms leading to poor proliferation and cell death of GATA-2-/- hematopoietic cells, we generated GATA2-/-/p53-/- compound-mutant embryos and investigated their hematopoietic potential. We demonstrate that the absence of p53 partially counteracts the hematopoietic defects of GATA-2-/- cells with respect to the number of total hematopoietic cells, a finding that suggests a potential link between the functions of GATA-2 and p53.
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MATERIALS AND METHODS |
Cells and culture conditions.
GATA-2-/- mutant ES cells were generated from CCE ES cells and wild-type and mutant ES cells were cultured as previously described.19
In vitro hematopoietic differentiation of ES cells.
Undifferentiated ES cells were first grown on gelatin-coated plates in the absence of feeder fibroblasts for at least three passages. ES cells collected from 30% to 50% confluent plates were washed with ES medium without leukemia inhibitory factor (or ESgro) and then used in in vitro hematopoietic differentiation analysis.19 For two-step in vitro differentiation, ES cells (1,000 to 2,000 per 3.5-cm dish) were first plated into methylcellulose medium containing KL and interleukin-11 (IL-11) to form embryoid bodies (EBs). Plating efficiencies for EB formation of wild-type and two independent GATA-2-/- ES clones on primary plates were similar. Disaggregated cells (105/3.5-cm dish) from day 5 to day 15 EBs were replated into media containing various combinations of growth factors.20 The hematopoietic colonies grown on secondary plates were examined.
GATA-2-/- inbred embryos and GATA-2/p53 compound-mutant embryos.
Germline transmitting chimeras produced by injecting GATA-2+/- cells into C57/B6 blastocysts were mated with 129/Sv female mice to generate 129/Sv inbred GATA-2+/- mice. 129/Sv inbred GATA-2-/- embryos were generated by crossing the GATA-2+/- inbred mice. For generating GATA-2/p53 compound-mutant mice, GATA-2+/- mice19 were crossed with p53+/- mice21 to generate GATA-2+/-/p53+/- compound-heterozygous mice. Embryos from intercrossing GATA-2+/-/p53+/- male and female mice were analyzed at E9-E10.
Yolk sac colony assay and in vitro liquid culture.
Hematopoietic cells from E9-E10 yolk sacs were collected as previously described.19 One third of the total yolk sac cells were plated into medium containing KL, IL-3, IL-11, and erythopoietin (Epo). Hematopoietic colonies were examined and counted after day 6. For in vitro liquid culture, yolk sac cells were cultured in liquid medium containing KL, IL-3, IL-11, and Epo. Hematopoietic cells from colony assay and in vitro liquid culture were cytocentrifuged onto slides and stained with May-Grünwald/Giemsa or Toluidine blue for morphologic examination.
Reverse-transcriptase-polymerase chain reaction (RT-PCR) analyses.
RNAs were isolated from hematopoietic colonies with RNAzole (TEL-Test Inc, Friendswood, TX). The RT-PCR and primers used for detecting specific mRNAs were as described previously.10
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RESULTS |
Establishment of a two-step in vitro hematopoietic differentiation assay for hematopoietic multipotential progenitors.
To examine the effect of GATA-2 loss on hematopoietic multipotential progenitors more directly, we used a two-step in vitro ES cell differentiation assay. Specifically, we disaggregated wild-type EBs, grown in medium containing KL and IL-11, at selected times and replated the cells in the presence of different combinations of growth factors including KL, IL-3, IL-6, IL-11, granulocyte-macrophage colony-stimulating factor, and Epo. Our aim was to identify experimental conditions that favored the expansion and maintenance of hematopoietic progenitors, rather than the appearance of single-lineage committed colonies. In Table 1, the formation of hematopoietic colonies is compared between two media conditions (KL, IL-3, IL-11, and Epo v KL plus Epo) for secondary plates. The number of colonies containing cells of single lineage reflects the number of committed precursors in the original EBs, and the number of mixed or blast colonies provides a measurement of the number of multipotential hematopoietic progenitors in the EBs. We found that the minimum cytokine combination needed for the growth of hematopoietic progenitors includes KL, IL-3, and IL-11. Addition of Epo permits production of mature erythroid cells. In agreement with a previous finding,20 KL plus Epo favors the formation of erythroid cells at the expense of uncommitted progenitors.
Mixed or blast cell colonies are greatly reduced in number and size from GATA-2-/- ES cells.
We next examined the behavior of GATA-2-/- ES cells under in vitro differentiation conditions favoring the development and maintenance of multipotential progenitors. The total number of hematopoietic colonies derived from GATA-2-/- cells disaggregated from day 9 EBs was reduced by approximately fourfold (Table 2). However, of particular note, the most profound deficit is displayed in mixed or blast cell colonies (mix/blast colonies) derived from uncommitted progenitors, which are disproportionately underrepresented upon replating of GATA-2-/- cells (1.6% of total colonies). Among colonies derived from committed precursors, non-red/G colonies (mostly mast cell colonies) were also markedly reduced in proportion (3.2% of total colonies). Nonetheless, the proportion of erythroid and macrophage colonies is not significantly altered as compared with wild-type cells.
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Table 2.
Two-Step In Vitro Differentiation of Wild-Type and GATA-2-/- ES Cells (colonies/105 cells in secondary plates)
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In addition to the disproportionate loss of mix/blast colonies, the few colonies observed are small and appear to contain dying cells (Figs 1 and 2). Similar results were observed upon replating of GATA-2-/- EBs at earlier times (days 5 and 7; data not shown). However, only macrophages and a few erythroid colonies appeared in secondary plates when cells from day 12 GATA-2-/- EBs were replated (data not shown). These findings from in vitro culture demonstrate that the defect in GATA-2-/- cells is manifested at early developmental stages in multipotential progenitors rather than in committed erythroid or myeloid precursors.
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| Fig 1.
Mixed or blast-type hematopoietic colonies derived from wild-type and GATA-2-/- ES cells in the 2-step in vitro differentiation assay. Day 9 EBs were disaggregated and plated into secondary plates with medium containing KL, IL-3, IL-11, and Epo. Mixed and blast-type hematopoietic colonies of wild-type origin (A and C) or GATA-2-/- (B and D) origin were examined on day 9 (A and B) and day 13 (C and D). This finding was reproduced in 2 experiments using 2 independent GATA-2-/- clones.
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| Fig 2.
Morphology of mixed and blast-type colonies shown in Fig 1C and D. Cells from single mix/blast colonies shown in Fig 1C (A, wild-type) and D (B, GATA-2-/-) were examined by May-Giemsa staining. e, erythroid cell; mc, macrophage; n, neutrophil; mg, megakaryocyte.
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GATA-2 is dispensable for terminal differentiation of erythroid cells and macrophages.
In contrast to the abnormal appearance of GATA-2-/- mix/blast colonies, erythroid and macrophage colonies of GATA-2-/- origin are similar in morphology to those of wild-type origin (Fig 3). To confirm the visual impression of normal erythroid maturation in the absence of GATA-2, RT-PCR analysis was used to estimate the expression of  -globin and GATA-1 in GATA-2-/- derived erythroid colonies. The results in Fig 4, demonstrate that RNA transcript levels for GATA-1 and globin (as compared with either actin or hypoxanthine phosphoribosyltransferase internal control) are normal in GATA-2-/- erythroid colonies. Consistent with this finding, the level of  and  -globin mRNAs per cell is also normal in GATA-2-/- yolk sac erythroid cells at E10 (data not shown). Thus, erythroid and macrophage precursors develop normally in the absence of GATA-2.
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| Fig 3.
Primitive erythroid, definitive erythroid, and macrophage colonies derived from wild-type and GATA-2-/- ES cells in the 2-step in vitro differentiation. Day 9 EBS were disaggregated and plated into secondary plates with medium containing KL, IL-3, IL-11, and Epo. Colonies with cells of single lineages of wild-type origin (A, C, and E) and GATA-2-/- origin (B, D, and F ) were compared. Primitive erythroid colonies (A and B), definitive erythroid colonies (C and D), and macrophage colonies (E and F ) were examined on days 5, 6, and 13, respectively.
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| Fig 4.
Comparison of -globin and GATA-1 expression levels in wild-type versus GATA-2-/- definitive erythroid cells. Levels of -globin and GATA-1 transcripts in definitive erythroid cells of wild-type colonies (1 and 2) and GATA-2-/- colonies (3 and 4) were compared by RT-PCR analysis with 2 different PCR cycles. Lanes 1 and 3, 24 PCR cycles for -globin and 32 PCR cycles for GATA-1; lanes 2 and 4, 26 PCR cycles for -globin and 34 PCR cycles for GATA-1. Actin and HPRT were used as internal controls for -globin and GATA-1 expression, respectively.
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Hematopoietic cells from inbred GATA-2-/- yolk sac at E9.5-E10 contain few multipotential progenitors with poor expansion capacity and fail to generate mast cells upon in vitro culture.
To evaluate whether the in vitro findings reflect the in vivo situation, we next examined the hematopoietic progenitor pool and mast cell formation of GATA-2-/- yolk sac hematopoietic cells in an inbred background. 129/Sv inbred GATA-2-/- embryos die at a similar stage as the 129/C57B6 outbred GATA-2-/- embryos studied previously.19 To examine the multipotential progenitor pool, cell suspensions were made from E9.5-E10 GATA-2-/- yolk sacs and plated in methylcellulose medium containing KL, IL-3, IL-11, and Epo. In agreement with our in vitro differentiation results already shown and colony assays performed previously on the 129/C57B6 outbred strain,19 the total number of colonies is reduced approximately 10-fold in GATA-2-/- relative to wild-type yolk sac, with the most profound deficit evident in mix/blast colonies (Table 3). Moreover, the few GATA-2-/- progenitors that are detected give rise to extremely small colonies that contain dying cells (Fig 5). Together, these results indicate that the loss of GATA-2 adversely affects both the number and the quality of multipotential hematopoietic progenitors in vivo.
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| Fig 5.
Mixed and blast-type hematopoietic colonies derived from wild-type and GATA-2-/- yolk sac cells at E9.5. Cells collected from the yolk sac at E9.5 were subjected to progenitor assay using medium containing KL, IL-11, IL-3, and Epo. Mixed and blast-type colonies from wild-type (A and C) and GATA-2-/- (B and D) cells were examined on day 9 in culture. This finding was reproduced in 4 GATA-2-/- embryos analyzed from 2 litters.
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To examine mast cell formation, we performed long-term yolk sac culture in media containing KL and IL-3. After in vitro culture for longer than 3 weeks, wild-type yolk sac cells give rise to mainly macrophages and mast cells (Fig 6A). However, GATA-2-/- yolk sac cells generate only macrophages (Fig 6B). This observation is consistent with the results of the in vitro differentiation assay and indicates a critical role for GATA-2 in mast cell formation.
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| Fig 6.
Mast cell formation in liquid culture of yolk sac cells. Yolk sac cells collected at E9.5 were subjected to long-term in vitro liquid culture with KL and IL-3 for mast cell formation. Mast cell formation from wild-type cells (A) and GATA-2-/- cells (B) was examined by Toluidine blue staining after 3 weeks in culture. mc, macrophage; m, mast cell. This finding was reproduced in 3 independent experiments.
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The hematopoietic defects of GATA-2-/- cells are partially reversed by the absence of p53.
To investigate a potential role of p53 in mediating the phenotypes of GATA-2-/- hematopoietic cells, we generated and characterized GATA-2-/-/p53-/- compound-mutant embryos. Among 53 2-week-old offsprings from intercrossing of GATA-2+/-/p53+/- male and female mice, no GATA-2-/- mice (with or without p53 mutation) were found. Thus, GATA-2-/- mice are embryonic-lethal, independent of the presence or absence of p53 (Table 4). For embryos analyzed at E9-E9.5, all potential genotypes were observed at approximately the expected frequency (Table 4). At E9-E9.5, GATA-2-/-/p53+/+, GATA-2-/-/p53+/-, and GATA-2-/-/p53-/- embryos were still alive with detectable circulating blood (data not shown).
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Table 4.
Genotype Analysis of E9-E9.5 Embryos and 2-Week-Old Mice Generated From GATA-2+/-/p53+/- Compound
Heterozygous Mice
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Since our results reveal profound hematopoietic deficits of GATA-2-/- cells in terms of multipotential progenitors and mast cell lineage, we performed in vitro hematopoietic culture of yolk sac cells from GATA-2-/-/p53-/- compound mutants to examine the effect of p53 loss on the hematopoietic defects of GATA-2-/- cells. In the liquid culture system with KL, IL-3, IL-11, and Epo, wild-type cells give rise to various types of hematopoietic cells, including definitive erythroid cells, macrophages, mast cells, megakaryocytes, and neutrophils (Fig 7). However, GATA-2-/-/p53+/+ cells generate only macrophages and erythroid cells (Fig 7) with a total cell number of approximately 5% of their wild-type counterpart (Table 5). In a GATA-2+/+ or GATA-2+/- background, the absence of p53 has no significant effect on cell number (Table 5) or cell composition (Fig 7) of hematopoietic populations in culture. However, loss of p53 leads to a significant enhancement (~fourfold) in the number of total hematopoietic cells derived from GATA-2-/- yolk sac cells in liquid culture (Table 5). Furthermore, GATA-2-/-/p53-/- cells give rise to definitive erythroid cells, macrophages, megakaryocytes, and neutrophils, but no mast cells (Fig 7). Colony assays were also performed to further characterize the hematopoietic progenitors and precursors in GATA2-/-/p53-/- yolk sac cells. The absence of p53 in the GATA-2-/- background results in an increase of total colony number of approximately 2.5-fold (Table 6), an observation consistent with the increased cell number seen upon liquid culture (Table 5). Nonetheless, the GATA-2-/-/p53-/- yolk sac cells still fail to generate large mixed or blast-type hematopoietic colonies (data not shown), suggesting that p53 might be more critical for survival than for proliferation of GATA-2-/- hematopoietic cells.
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| Fig 7.
Hematopoietic potential of yolk sac cells with various genotypes. Yolk sac cells collected at E9.5 were subjected to in vitro liquid culture with KL, IL-11, IL-3, and Epo. Hematopoietic cells grown after 10 days in culture were cytocentrifuged onto slides and stained with May-Grünwald/Giemsa. The arrow points to mast cells.
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DISCUSSION |
In this study, we focused our attention on the progenitor pool and specifically distinguished the effects of GATA-2 loss on multipotential progenitors versus those on maturation of specific lineages. Multipotential hematopoietic progenitors obtained from GATA-2-/- yolk sac and GATA-2-/- in vitro differentiating EBs are greatly reduced in number relative to wild-type controls. Moreover, GATA-2-/- mixed or blast cell colonies derived from uncommitted progenitors were qualitatively different, as exemplified by their small size and the presence of dying cells. The impact of GATA-2 loss on hematopoietic progenitors is likely to be complex and includes disturbances of cellular proliferation and survival, as well as possible effects on the life span of progenitors or their capacity to maintain an uncommitted phenotype.
Mast cells are not present in long-term cultures of GATA-2-/- yolk sac cells. Two points suggest that GATA-2 may play a particularly important role in the expansion of mast cell precursors. First, the number of GATA-2-/- mast cell precursors is decreased to a far greater extent than the number of erythroid or macrophage precursors. Second, GATA-2 expression is largely restricted to proliferating mast cells.22 Nonetheless, GATA-2 may also function in the differentiation of mast cells, because no mature mast cells were obtained from GATA-2-/- cells in long-term yolk sac culture. These findings are consistent with the coexpression of GATA-1 and GATA-2 in mast cells and the formation of mast cells in the absence of GATA-1,23 and also suggest a specific function for GATA-2 in the production of mast cells.
Our experiments also allow us to conclude that loss of GATA-2 per se does not appear to affect maturation along erythroid or macrophage lineages. The observed decrease in the number of committed precursors for these lineages in GATA-2-/- EBs is best interpreted as an indirect consequence of deficits in the uncommitted, multipotential progenitors. After commitment to either lineage takes place, terminal differentiation of erythroid cells and macrophages can proceed in the absence of GATA-2. Comparison of specific mRNAs in wild-type and GATA-2-/- erythroid colonies is consistent with this view and shows that GATA-2 is not required for transcription of GATA-1 or globin genes in committed erythroid cells. Moreover, GATA-2 seems dispensable in lymphoid development and terminal differentiation of neutrophils, as indicated by the presence of occasional GATA-2-/- mature T cells in chimeras made with RAG-2-deficient blastocyts19 and the formation of some neutrophils upon in vitro culture of GATA-2-/- yolk sac cells (data not shown).
The status of HSCs in GATA-2-/- EBs and embryos is difficult to assess because of the low number of such cells even in wild-type embryos. The fact that mature blood cells are detectable both in vivo and in vitro with GATA-2-/- background clearly indicates that stem cells are formed, but it is still unclear whether GATA-2-/- stem cells are able to self-renew and survive normally. Alternative approaches such as conditional gene targeting might clarify the specific function of GATA-2 in HSCs.
The few GATA-2-/- multipotential hematopoietic progenitors in early embryos and EBs have low proliferative capacity, and cells derived from them are prone to die during in vitro culture. These findings strongly suggest that GATA-2 functions in the proliferation and survival of early hematopoietic cells. Among the factors controlling cell proliferation and survival, the tumor suppresser p53 acts as a negative regulator to prevent the expansion of specific cell populations by triggering cell-cycle arrest and apoptosis.24-27 p53 is frequently mutated in a variety of human cancers, including leukemia.28,29 A large proportion of mice lacking p53 are viable with high tumor susceptibility.21,30,31 However, some p53-null mouse embryos die in uteri with abnormal neural tube development.32 In hematopoiesis, apoptosis appears to play a role in controlling the number of early hematopoietic cells,33 and p53 has been shown to be involved in the induction of apoptosis in the hematopoietic cell line M1.34 In addition, the fact that p53-null hematopoietic cells can be immortalized by expressing raf or myc-raf oncogenes without additional genetic alternation implies a crucial role of p53 as a barrier for active proliferation of hematopoietic cells.35 The difference in hematopoietic potential between GATA-2-/-/p53+/+ and GATA-2-/-/p53-/- cells implies that wild-type p53 might play a role in triggering senescence and/or cell death of GATA-2-/- hematopoietic cells. Additionally, with an increase in the number of total hematopoietic cells, we were able to detect numerous macrophages, erythroid cells, megakaryocytes, and neutropils derived from GATA-2-/-/p53-/- cells, demonstrating again that GATA-2 is not strictly required for development of these cells. The absence of mast cells in the GATA-2-/-/p53-/- hematopoietic population further confirms a crucial role of GATA-2 in mast cell formation.
The involvement of GATA-2 in expanding early hematopoietic cells contrasts with the requirement for the related factor GATA-1 in terminal erythroid maturation.10,36 The reciprocal expression of these factors during erythroid development parallels the shift from proliferation to terminal maturation. Although the apparent roles of these factors differ, GATA-1 and GATA-2 are coexpressed during much of erythroid and hematopoietic development. The maturation of erythroid precursors to the proerythroblast stage, coupled with the failure to repress GATA-2 levels in the absence of GATA-1,10,23 suggests that GATA-2 can partially fulfill some of the transcriptional roles of GATA-1. Accordingly, it is possible that GATA-1 expressed at low levels in early hematopoietic cells may compensate partially for the absence of GATA-2, which results in few surviving multipotential progenitors at early developmental stages. As such, early hematopoietic cells might be even more severely impaired, or perhaps unable to form, if all GATA factors were absent. Creation of ES cells or embryos lacking both GATA-1 and GATA-2 should permit a direct test of these possibilities.
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FOOTNOTES |
Submitted October 23, 1996;
accepted January 14, 1997.
Address reprint requests to Stuart H. Orkin, MD, Division of Hematology/Oncology, Children's Hospital, 300 Longwood Ave, Boston, MA 02115.
The publication costs of this article were defrayed in part by page
charge payment. This article must therefore be hearly marked
``advertisment'' in accordance with 18 U.S.C. section 1734 solely to
indicate this fact.
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REFERENCES |
1.
Ogawa M:
Differentiation and proliferation of hematopoietic stem cells.
Blood
81:2844,
1993[Abstract/Free Full Text]
2.
Metcalf D:
Hematopoietic regulators: Redundancy or subtlety?
Blood
82:3515,
1993[Free Full Text]
3.
Morrison SJ,
Uchida N,
Weissman IL:
The biology of hematopoietic stem cells.
Annu Rev Cell Dev Biol
11:35,
1995[Medline]
[Order article via Infotrieve]
4.
Orkin SH:
Transcription factors and hematopoietic development.
J Biol Chem
270:4955,
1995[Free Full Text]
5.
Shivdasani RA,
Orkin SH:
The transcriptional control of hematopoiesis.
Blood
87:4025,
1996[Free Full Text]
6.
Orkin SH:
GATA-binding transcription factors in hematopoietic cells.
Blood
80:575,
1992[Free Full Text]
7.
Weiss MJ,
Orkin SH:
GATA transcription factors: Key regulators of hematopoiesis.
Exp Hematol
23:99,
1995[Medline]
[Order article via Infotrieve]
8.
Tsai SF,
Martin DI,
Zon LI,
D'Andrea AD,
Wong GG,
Orkin SH:
Cloning of cDNA for the major DNA-binding protein of the erythroid lineage through expression in mammalian cells.
Nature
339:446,
1989[Medline]
[Order article via Infotrieve]
9.
Evans T,
Felsenfeld G:
The erythroid-specific transcription factor eryf1: A new finger protein.
Cell
58:877,
1989[Medline]
[Order article via Infotrieve]
10.
Weiss MJ,
Keller G,
Orkin SH:
Novel insights into erythroid development revealed through in vitro differentiation of GATA-1 embryonic stem cells.
Genes Dev
8:1184,
1994[Abstract/Free Full Text]
11.
Fujiwara Y,
Browne CP,
Cunniff K,
Goff S,
Orkin SH:
Arrested development of embryonic red cell precursors in mouse embryos lacking transcription factor GATA-1.
Proc Natl Acad Sci USA
93:12395,
1996
12.
Landry DB,
Engel JD,
Sen R:
Functional GATA-3 binding sites within murine CD8 alpha upstream regulatory sequences.
J Exp Med
178:941,
1993[Abstract/Free Full Text]
13.
Ko LJ,
Yamamoto M,
Leonard MW,
George KM,
Ting P,
Engel JD:
Murine and human T-lymphocyte GATA-3 factors mediate transcription through a cis-regulatory element within the human T-cell receptor delta gene enhancer.
Mol Cell Biol
11:2778,
1991[Abstract/Free Full Text]
14.
Ting C-N,
Olson MC,
Barton KP,
Leiden JM:
The GATA-3 transcription factor is required for the development of the T cell lineage.
Nature
384:474,
1996[Medline]
[Order article via Infotrieve]
15.
Dorfman DM,
Wilson DB,
Bruns GA,
Orkin SH:
Human transcription factor GATA-2. Evidence for regulation of preproendothelin-1 gene expression in endothelial cells.
J Biol Chem
267:1279,
1992[Abstract/Free Full Text]
16.
Visvader J,
Adams JM:
Megakaryocytic differentiation induced in 416B myeloid cells by GATA-2 and GATA-3 transgenes or 5-azacytidine is tightly coupled to GATA-1 expression.
Blood
82:1493,
1993[Abstract/Free Full Text]
17.
Leonard M,
Brice M,
Engel JD,
Papayannopoulou T:
Dynamics of GATA transcription factor expression during erythroid differentiation.
Blood
82:1071,
1993[Abstract/Free Full Text]
18.
Mouthon MA,
Bernard O,
Mitjavila MT,
Romeo PH,
Vainchenker W,
Mathieu-Mahul D:
Expression of tal-1 and GATA-binding proteins during human hematopoiesis.
Blood
81:647,
1993[Abstract/Free Full Text]
19.
Tsai FY,
Keller G,
Kuo FC,
Weiss M,
Chen J,
Rosenblatt M,
Alt FW,
Orkin SH:
An early haematopoietic defect in mice lacking the transcription factor GATA-2.
Nature
371:221,
1994[Medline]
[Order article via Infotrieve]
20.
Keller G,
Kennedy M,
Papayannopoulou T,
Wiles MV:
Hematopoietic commitment during embryonic stem cell differentiation in culture.
Mol Cell Biol
13:473,
1993[Abstract/Free Full Text]
21.
Jacks T,
Remington L,
Williams B,
Scmitt E,
Halachmi S,
Bronson R,
Weinberg R:
Tumor spectrum analysis in p53-mutant mice.
Curr Biol
4:1,
1994[Medline]
[Order article via Infotrieve]
22.
Jippo T,
Mizuno H,
Xu Z,
Nomura S,
Yamamoto M,
Kitamura Y:
Abundant expression of transcription factor GATA-2 in proliferating but not in differentiated mast cells in tissues of mice: Demonstration by in situ hybridization.
Blood
87:993,
1996[Abstract/Free Full Text]
23.
Pevny L,
Lin CS,
D'Agati V,
Simon MC,
Orkin SH,
Costantini F:
Development of hematopoietic cells lacking transcription factor GATA-1.
Development
121:163,
1995[Abstract]
24.
Donehower LA,
Bradley A:
The tumor suppressor p53.
Biochem Biophys Acta
1155:181,
1993[Medline]
[Order article via Infotrieve]
25.
Picksley SM,
Lane DP:
p53 and Rb: Their cellular roles.
Curr Opin Cell Biol
6:853,
1994[Medline]
[Order article via Infotrieve]
26.
Kastan MB,
Canman CE,
Leonard CJ:
p53, cell cycle control and apoptosis: Implications for cancer.
Cancer Metastasis Rev
14:3,
1995[Medline]
[Order article via Infotrieve]
27.
Polyak K,
Waldman T,
He T-C,
Kinzler KW,
Volgelstein B:
Genetic determinants of p53-induced apoptosis and growth arrest.
Genes Dev
10:1945,
1996[Abstract/Free Full Text]
28.
Lane DP:
p53, guardian of the genome.
Nature
358:15,
1992[Medline]
[Order article via Infotrieve]
29.
Greenblatt MS,
Bennett WP,
Hollstein M,
Harris CC:
Mutations in the p53 tumor suppressor gene: Clues to cancer etiology and molecular pathogenesis.
Cancer Res
54:4855,
1994[Free Full Text]
30.
Donehower LA,
Harvey M,
Slagle BL,
McArthur MJ,
Montgomery CAJ,
Butel JS,
Bradley A:
Mice deficient for p53 are developmentally normal but susceptible to spontaneous tumours.
Nature
356:215,
1992[Medline]
[Order article via Infotrieve]
31.
Purdie CA,
Harrison DJ,
Peter A,
Dobbie L,
White S,
Howie SEM,
Salter DM,
Bird CC,
Wyllie AH,
Hooper ML,
Clarke AR:
Tumour incidence, spectrum, and ploidy in mice with a large deletion in the p53 gene.
Oncogene
9:603,
1994[Medline]
[Order article via Infotrieve]
32.
Sah VP,
Attardi LD,
Murrigan GJ,
Williams BO,
Bronson RT,
Jacks T:
A subset of p53-deficient embryos exhibit exencephaly.
Nat Genet
10:175,
1995[Medline]
[Order article via Infotrieve]
33.
Williams GT,
Smith CA,
Spooncer E,
Dexter TM,
Taylor DR:
Haemapoietic colony stimulating factors promote cell survival by suppressing apoptosis.
Nature
343:76,
1990[Medline]
[Order article via Infotrieve]
34.
Yonish-Rouach E,
Resnitzky D,
Lotem J,
Sachs L,
Kimchi A,
Oren M:
Wild-type p53 induces apoptosis of myeloid leukaemic cells that is inhibited by interleukin-6.
Nature
352:345,
1991[Medline]
[Order article via Infotrieve]
35.
Metz T,
Harris AW,
Adams JM:
Absence of p53 allows direct immortalization of hematopoietic cells by the myc and raf oncogenes.
Cell
82:29,
1995[Medline]
[Order article via Infotrieve]
36.
Weiss MJ,
Orkin SH:
Transcription factor GATA-1 permits survival and maturation of erythroid precursors by preventing apoptosis.
Proc Natl Acad Sci USA
92:9623,
1995[Abstract/Free Full Text]
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|
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[Full Text]
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|
|
|
|
|
|
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[Full Text]
[PDF]
|
|
|
|
|
|
|
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Antagonism of FOG-1 and GATA factors in fate choice for the mast cell lineage
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205(3):
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[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J.-R. Landry, S. Kinston, K. Knezevic, M. F.T.R. de Bruijn, N. Wilson, W. T. Nottingham, M. Peitz, F. Edenhofer, J. E. Pimanda, K. Ottersbach, et al.
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[Full Text]
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|
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|
|
|
|
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105(9):
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[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
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February 15, 2008;
111(4):
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[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
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J. M. Salmon, N. J. Slater, M. A. Hall, M. P. McCormack, S. L. Nutt, S. M. Jane, and D. J. Curtis
Aberrant mast-cell differentiation in mice lacking the stem-cell leukemia gene
Blood,
November 15, 2007;
110(10):
3573 - 3581.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Y. Chen, P. Haviernik, K. D. Bunting, and Y.-C. Yang
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110(8):
2889 - 2898.
[Abstract]
[Full Text]
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|
|
|
|
|
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|
|
|
|
|
|
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September 15, 2007;
110(6):
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[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
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142(1):
1 - 10.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
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|
|
|
|
|
|
|
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May 15, 2007;
109(10):
4200 - 4208.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
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14665 - 14674.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Khandekar, W. Brandt, Y. Zhou, S. Dagenais, T. W. Glover, N. Suzuki, R. Shimizu, M. Yamamoto, K.-C. Lim, and J. D. Engel
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May 1, 2007;
134(9):
1703 - 1712.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. J. Lugus, Y. S. Chung, J. C. Mills, S.-I. Kim, J. A. Grass, M. Kyba, J. M. Doherty, E. H. Bresnick, and K. Choi
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January 15, 2007;
134(2):
393 - 405.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Masuda, K. Hashimoto, T. Yokoi, T. Doi, T. Kodama, H. Kume, K. Ohno, and T. Matsuguchi
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J. Immunol.,
January 1, 2007;
178(1):
360 - 368.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. H. Shahlaee, S. Brandal, Y.-N. Lee, C. Jie, and C. M. Takemoto
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J. Immunol.,
January 1, 2007;
178(1):
378 - 388.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. L. Martowicz, J. A. Grass, and E. H. Bresnick
GATA-1-mediated Transcriptional Repression Yields Persistent Transcription Factor IIB-Chromatin Complexes
J. Biol. Chem.,
December 8, 2006;
281(49):
37345 - 37352.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. Iwasaki, S.-i. Mizuno, Y. Arinobu, H. Ozawa, Y. Mori, H. Shigematsu, K. Takatsu, D. G. Tenen, and K. Akashi
The order of expression of transcription factors directs hierarchical specification of hematopoietic lineages.
Genes & Dev.,
November 1, 2006;
20(21):
3010 - 3021.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. D. Johnson, S.-I. Kim, and E. H. Bresnick
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October 24, 2006;
103(43):
15939 - 15944.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. Laricchia-Robbio, R. Fazzina, D. Li, C. R. Rinaldi, K. K. Sinha, S. Chakraborty, and G. Nucifora
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October 15, 2006;
26(20):
7658 - 7666.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. A. Grass, H. Jing, S.-I. Kim, M. L. Martowicz, S. Pal, G. A. Blobel, and E. H. Bresnick
Distinct Functions of Dispersed GATA Factor Complexes at an Endogenous Gene Locus.
Mol. Cell. Biol.,
October 1, 2006;
26(19):
7056 - 7067.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Z. Yuan, A. Tie, M. Tarnopolsky, and M. Bakovic
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Physiol Genomics,
September 14, 2006;
26(1):
76 - 90.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Vegiopoulos, P. Garcia, N. Emambokus, and J. Frampton
Coordination of erythropoiesis by the transcription factor c-Myb
Blood,
June 15, 2006;
107(12):
4703 - 4710.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. A. Charles, T. L. Saunders, W. M. Wood, K. Owens, A. F. Parlow, S. A. Camper, E. C. Ridgway, and D. F. Gordon
Pituitary-Specific Gata2 Knockout: Effects on Gonadotrope and Thyrotrope Function
Mol. Endocrinol.,
June 1, 2006;
20(6):
1366 - 1377.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. F. de Pooter, T. M. Schmitt, J. L. de la Pompa, Y. Fujiwara, S. H. Orkin, and J. C. Zuniga-Pflucker
Notch Signaling Requires GATA-2 to Inhibit Myelopoiesis from Embryonic Stem Cells and Primary Hemopoietic Progenitors
J. Immunol.,
May 1, 2006;
176(9):
5267 - 5275.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. Kitajima, M. Tanaka, J. Zheng, H. Yen, A. Sato, D. Sugiyama, H. Umehara, E. Sakai, and T. Nakano
Redirecting differentiation of hematopoietic progenitors by a transcription factor, GATA-2
Blood,
March 1, 2006;
107(5):
1857 - 1863.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
N. Suzuki, O. Ohneda, N. Minegishi, M. Nishikawa, T. Ohta, S. Takahashi, J. D. Engel, and M. Yamamoto
Combinatorial Gata2 and Sca1 expression defines hematopoietic stem cells in the bone marrow niche
PNAS,
February 14, 2006;
103(7):
2202 - 2207.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. C. Tang, J. Zhu, W. Liu, K. Chin, J. Sun, L. Chen, J. A. Hanover, and G. P. Rodgers
The hydroxyurea-induced small GTP-binding protein SAR modulates {gamma}-globin gene expression in human erythroid cells
Blood,
November 1, 2005;
106(9):
3256 - 3263.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
N. P. Rodrigues, V. Janzen, R. Forkert, D. M. Dombkowski, A. S. Boyd, S. H. Orkin, T. Enver, P. Vyas, and D. T. Scadden
Haploinsufficiency of GATA-2 perturbs adult hematopoietic stem-cell homeostasis
Blood,
July 15, 2005;
106(2):
477 - 484.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
N. Minegishi, N. Suzuki, Y. Kawatani, R. Shimizu, and M. Yamamoto
Rapid turnover of GATA-2 via ubiquitin-proteasome protein degradation pathway
Genes Cells,
July 1, 2005;
10(7):
693 - 704.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. Manfredini, R. Zini, S. Salati, M. Siena, E. Tenedini, E. Tagliafico, M. Montanari, T. Zanocco-Marani, C. Gemelli, T. Vignudelli, et al.
The Kinetic Status of Hematopoietic Stem Cell Subpopulations Underlies a Differential Expression of Genes Involved in Self-Renewal, Commitment, and Engraftment
Stem Cells,
April 1, 2005;
23(4):
496 - 506.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Ezoe, I. Matsumura, K. Gale, Y. Satoh, J. Ishikawa, M. Mizuki, S. Takahashi, N. Minegishi, K. Nakajima, M. Yamamoto, et al.
GATA Transcription Factors Inhibit Cytokine-dependent Growth and Survival of a Hematopoietic Cell Line through the Inhibition of STAT3 Activity
J. Biol. Chem.,
April 1, 2005;
280(13):
13163 - 13170.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Robert-Moreno, L. Espinosa, J. L. de la Pompa, and A. Bigas
RBPj{kappa}-dependent Notch function regulates Gata2 and is essential for the formation of intra-embryonic hematopoietic cells
Development,
March 1, 2005;
132(5):
1117 - 1126.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. I. Marusina, D.-K. Kim, L. D. Lieto, F. Borrego, and J. E. Coligan
GATA-3 Is an Important Transcription Factor for Regulating Human NKG2A Gene Expression
J. Immunol.,
February 15, 2005;
174(4):
2152 - 2159.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. L. Martowicz, J. A. Grass, M. E. Boyer, H. Guend, and E. H. Bresnick
Dynamic GATA Factor Interplay at a Multicomponent Regulatory Region of the GATA-2 Locus
J. Biol. Chem.,
January 21, 2005;
280(3):
1724 - 1732.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. J. Nemeth, A. P. Cline, S. M. Anderson, L. J. Garrett-Beal, and D. M. Bodine
Hmgb3 deficiency deregulates proliferation and differentiation of common lymphoid and myeloid progenitors
Blood,
January 15, 2005;
105(2):
627 - 634.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Khandekar, N. Suzuki, J. Lewton, M. Yamamoto, and J. D. Engel
Multiple, Distant Gata2 Enhancers Specify Temporally and Tissue-Specific Patterning in the Developing Urogenital System
Mol. Cell. Biol.,
December 1, 2004;
24(23):
10263 - 10276.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K.-W. Ling, K. Ottersbach, J. P. van Hamburg, A. Oziemlak, F.-Y. Tsai, S. H. Orkin, R. Ploemacher, R. W. Hendriks, and E. Dzierzak
GATA-2 Plays Two Functionally Distinct Roles during the Ontogeny of Hematopoietic Stem Cells
J. Exp. Med.,
October 4, 2004;
200(7):
871 - 882.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. Summer, D. N. Kotton, X. Sun, K. Fitzsimmons, and A. Fine
Origin and phenotype of lung side population cells
Am J Physiol Lung Cell Mol Physiol,
September 1, 2004;
287(3):
L477 - L483.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Monticelli, D. C. Solymar, and A. Rao
Role of NFAT Proteins in IL13 Gene Transcription in Mast Cells
J. Biol. Chem.,
August 27, 2004;
279(35):
36210 - 36218.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Pal, M. J. Nemeth, D. Bodine, J. L. Miller, J. Svaren, S. L. Thein, P. J. Lowry, and E. H. Bresnick
Neurokinin-B Transcription in Erythroid Cells: DIRECT ACTIVATION BY THE HEMATOPOIETIC TRANSCRIPTION FACTOR GATA-1
J. Biol. Chem.,
July 23, 2004;
279(30):
31348 - 31356.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. Lahlil, E. Lecuyer, S. Herblot, and T. Hoang
SCL Assembles a Multifactorial Complex That Determines Glycophorin A Expression
Mol. Cell. Biol.,
February 15, 2004;
24(4):
1439 - 1452.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Pal, A. B. Cantor, K. D. Johnson, T. B. Moran, M. E. Boyer, S. H. Orkin, and E. H. Bresnick
Coregulator-dependent facilitation of chromatin occupancy by GATA-1
PNAS,
January 27, 2004;
101(4):
980 - 985.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Gurbuxani, P. Vyas, and J. D. Crispino
Recent insights into the mechanisms of myeloid leukemogenesis in Down syndrome
Blood,
January 15, 2004;
103(2):
399 - 406.
[Abstract]
[Full Text]
[PDF]
|
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|
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Y. Fujiwara, A. N. Chang, A. M. Williams, and S. H. Orkin
Functional overlap of GATA-1 and GATA-2 in primitive hematopoietic development
Blood,
January 15, 2004;
103(2):
583 - 585.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. G. Katz, A. Williams, J. Yang, Y. Fujiwara, A. P. Tsang, J. A. Epstein, and S. H. Orkin
Endothelial lineage-mediated loss of the GATA cofactor Friend of GATA 1 impairs cardiac development
PNAS,
November 25, 2003;
100(24):
14030 - 14035.
[Abstract]
[Full Text]
[PDF]
|
|
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|
|
|
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M. E. Lasbury, X. Tang, P. J. Durant, and C.-H. Lee
Effect of Transcription Factor GATA-2 on Phagocytic Activity of Alveolar Macrophages from Pneumocystis carinii-Infected Hosts
Infect. Immun.,
September 1, 2003;
71(9):
4943 - 4952.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
N. Minegishi, N. Suzuki, T. Yokomizo, X. Pan, T. Fujimoto, S. Takahashi, T. Hara, A. Miyajima, S.-i. Nishikawa, and M. Yamamoto
Expression and domain-specific function of GATA-2 during differentiation of the hematopoietic precursor cells in midgestation mouse embryos
Blood,
August 1, 2003;
102(3):
896 - 905.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
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J. A. Grass, M. E. Boyer, S. Pal, J. Wu, M. J. Weiss, and E. H. Bresnick
GATA-1-dependent transcriptional repression of GATA-2 via disruption of positive autoregulation and domain-wide chromatin remodeling
PNAS,
July 22, 2003;
100(15):
8811 - 8816.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Y. J. Suzuki, R. M. Day, C. C. Tan, T. H. Sandven, Q. Liang, J. D. Molkentin, and B. L. Fanburg
Activation of GATA-4 by Serotonin in Pulmonary Artery Smooth Muscle Cells
J. Biol. Chem.,
May 2, 2003;
278(19):
17525 - 17531.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. E. Lasbury, P. J. Durant, M. S. Bartlett, J. W. Smith, and C.-H. Lee
Correlation of Organism Burden and Alveolar Macrophage Counts during Infection with Pneumocystis carinii and Recovery
Clin. Vaccine Immunol.,
March 1, 2003;
10(2):
293 - 302.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. R. Migliaccio, R. A. Rana, M. Sanchez, R. Lorenzini, L. Centurione, L. Bianchi, A. M. Vannucchi, G. Migliaccio, and S. H. Orkin
GATA-1 as a Regulator of Mast Cell Differentiation Revealed by the Phenotype of the GATA-1low Mouse Mutant
J. Exp. Med.,
February 3, 2003;
197(3):
281 - 296.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Y. Kim, A.-G. Ma, K. Kitta, S. N. Fitch, T. Ikeda, Y. Ihara, A. R. Simon, T. Evans, and Y. J. Suzuki
Anthracycline-Induced Suppression of GATA-4 Transcription Factor: Implication in the Regulation of Cardiac Myocyte Apoptosis
Mol. Pharmacol.,
February 1, 2003;
63(2):
368 - 377.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
B. Liu, Y. Sun, F. Jiang, S. Zhang, Y. Wu, Y. Lan, X. Yang, and N. Mao
Disruption of Smad5 gene leads to enhanced proliferation of high-proliferative potential precursors during embryonic hematopoiesis
Blood,
January 1, 2003;
101(1):
124 - 133.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Ezoe, I. Matsumura, S. Nakata, K. Gale, K. Ishihara, N. Minegishi, T. Machii, T. Kitamura, M. Yamamoto, T. Enver, et al.
GATA-2/estrogen receptor chimera regulates cytokine-dependent growth of hematopoietic cells through accumulation of p21WAF1 and p27Kip1 proteins
Blood,
November 15, 2002;
100(10):
3512 - 3520.
[Abstract]
[Full Text]
[PDF]
|
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|
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Y.-L. Yu, Y.-J. Chiang, and J. J. Y. Yen
GATA Factors Are Essential for Transcription of the Survival Gene E4bp4 and the Viability Response of Interleukin-3 in Ba/F3 Hematopoietic Cells
J. Biol. Chem.,
July 19, 2002;
277(30):
27144 - 27153.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
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A. N. Chang, A. B. Cantor, Y. Fujiwara, M. B. Lodish, S. Droho, J. D. Crispino, and S. H. Orkin
GATA-factor dependence of the multitype zinc-finger protein FOG-1 for its essential role in megakaryopoiesis
PNAS,
July 9, 2002;
99(14):
9237 - 9242.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
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A. B. Cantor, S. G. Katz, and S. H. Orkin
Distinct Domains of the GATA-1 Cofactor FOG-1 Differentially Influence Erythroid versus Megakaryocytic Maturation
Mol. Cell. Biol.,
June 15, 2002;
22(12):
4268 - 4279.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. McNagny and T. Graf
Making Eosinophils Through Subtle Shifts in Transcription Factor Expression
J. Exp. Med.,
June 3, 2002;
195(11):
F43 - F47.
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Ghatpande, A. Ghatpande, J. Sher, M. H. Zile, and T. Evans
Retinoid signaling regulates primitive (yolk sac) hematopoiesis
Blood,
April 1, 2002;
99(7):
2379 - 2386.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. J. Morrison, D. Qian, L. Jerabek, B. A. Thiel, I.-K. Park, P. S. Ford, M. J. Kiel, N. J. Schork, I. L. Weissman, and M. F. Clarke
A Genetic Determinant That Specifically Regulates the Frequency of Hematopoietic Stem Cells
J. Immunol.,
January 15, 2002;
168(2):
635 - 642.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Y. Ozawa, M. Towatari, S. Tsuzuki, F. Hayakawa, T. Maeda, Y. Miyata, M. Tanimoto, and H. Saito
Histone deacetylase 3 associates with and represses the transcription factor GATA-2
Blood,
October 1, 2001;
98(7):
2116 - 2123.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. A. Shivdasani
Molecular and Transcriptional Regulation of Megakaryocyte Differentiation
Stem Cells,
September 1, 2001;
19(5):
397 - 407.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. M. Vannucchi, L. Bianchi, C. Cellai, F. Paoletti, V. Carrai, A. Calzolari, L. Centurione, R. Lorenzini, C. Carta, E. Alfani, et al.
Accentuated response to phenylhydrazine and erythropoietin in mice genetically impaired for their GATA-1 expression (GATA-1low mice)
Blood,
May 15, 2001;
97(10):
3040 - 3050.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
B. D. Car and V. M. Eng
Special Considerations in the Evaluation of the Hematology and Hemostasis of Mutant Mice
Vet. Pathol.,
January 1, 2001;
38(1):
20 - 30.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
E. E. Morrisey
GATA-6: The Proliferation Stops Here : Cell Proliferation in Glomerular Mesangial and Vascular Smooth Muscle Cells
Circ. Res.,
October 13, 2000;
87(8):
638 - 640.
[Full Text]
[PDF]
|
|
|
|
|
|
|
T.-X. Liu, J.-W. Zhang, J. Tao, R.-B. Zhang, Q.-H. Zhang, C.-J. Zhao, J.-H. Tong, M. Lanotte, S. Waxman, S.-J. Chen, et al.
Gene expression networks underlying retinoic acid-induced differentiation of acute promyelocytic leukemia cells
Blood,
August 15, 2000;
96(4):
1496 - 1504.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. E. Deconinck, P. E. Mead, S. G. Tevosian, J. D. Crispino, S. G. Katz, L. I. Zon, and S. H. Orkin
FOG acts as a repressor of red blood cell development in Xenopus
Development,
May 15, 2000;
127(10):
2031 - 2040.
[Abstract]
[PDF]
|
|
|
|
|
|
|
T. Lebestky, T. Chang, V. Hartenstein, and U. Banerjee
Specification of Drosophila Hematopoietic Lineage by Conserved Transcription Factors
Science,
April 7, 2000;
288(5463):
146 - 149.
[Abstract]
[Full Text]
|
|
|
|
|
|
|
S. Delassus, I. Titley, and T. Enver
Functional and Molecular Analysis of Hematopoietic Progenitors Derived From the Aorta-Gonad-Mesonephros Region of the Mouse Embryo
Blood,
September 1, 1999;
94(5):
1495 - 1503.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Holmes, J. Turner, A. Fox, O. Chisholm, M. Crossley, and B. Chong
hFOG-2, a Novel Zinc Finger Protein, Binds the Co-repressor mCtBP2 and Modulates GATA-mediated Activation
J. Biol. Chem.,
August 13, 1999;
274(33):
23491 - 23498.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. Heyworth, K. Gale, M. Dexter, G. May, and T. Enver
A GATA-2/estrogen receptor chimera functions as a ligand-dependent negative regulator of self-renewal
Genes & Dev.,
July 15, 1999;
13(14):
1847 - 1860.
[Abstract]
[Full Text]
|
|
|
|
|
|
|
D. A. Persons, J. A. Allay, E. R. Allay, R. A. Ashmun, D. Orlic, S. M. Jane, J. M. Cunningham, and A. W. Nienhuis
Enforced Expression of the GATA-2 Transcription Factor Blocks Normal Hematopoiesis
Blood,
January 15, 1999;
93(2):
488 - 499.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M.-C. Labastie, F. Cortes, P.-H. Romeo, C. Dulac, and B. Peault
Molecular Identity of Hematopoietic Precursor Cells Emerging in the Human Embryo
Blood,
November 15, 1998;
92(10):
3624 - 3635.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Z. Wang and S. Melmed
Functional Map of a Placenta-specific Enhancer of the Human Leukemia Inhibitory Factor Receptor Gene
J. Biol. Chem.,
October 2, 1998;
273(40):
26069 - 26077.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. L. Orford, C. Robinson, J. M. Haydon, R. K. Patient, and M. J. Guille
The Maternal CCAAT Box Transcription Factor Which Controls GATA-2 Expression Is Novel and Developmentally Regulated and Contains a Double-Stranded-RNA-Binding Subunit
Mol. Cell. Biol.,
September 1, 1998;
18(9):
5557 - 5566.
[Abstract]
[Full Text]
|
|
|
|
|
|
|
A. P. Tsang, Y. Fujiwara, D. B. Hom, and S. H. Orkin
Failure of megakaryopoiesis and arrested erythropoiesis in mice lacking the GATA-1 transcriptional cofactor FOG
Genes & Dev.,
April 15, 1998;
12(8):
1176 - 1188.
[Abstract]
[Full Text]
|
|
|
|
|
|
|
P. Mead, C. Kelley, P. Hahn, O Piedad, and L. Zon
SCL specifies hematopoietic mesoderm in Xenopus embryos
Development,
January 7, 1998;
125(14):
2611 - 2620.
[Abstract]
[PDF]
|
|
|
|
|
|
|
C. Lancrin, E. Schneider, F. Lambolez, M.-L. Arcangeli, C. Garcia-Cordier, B. Rocha, and S. Ezine
Major T Cell Progenitor Activity in Bone Marrow-derived Spleen Colonies
J. Exp. Med.,
April 1, 2002;
195(7):
919 - 929.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
Abstract
Introduction
Abstract