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HEMATOPOIESIS
From the Department of Medicine III,
Ludwig-Maximilians-University and GSF-National Research Center for
Environment and Health, Munich, Germany; Department of Immunology,
Institute of Basic Medical Sciences, University of Tsukuba Ibaraki,
Japan; and Harvard Institutes of Medicine, Harvard Medical School,
Boston, MA.
Several transcription factors have been implicated as playing a
role in myelopoiesis. PU.1, an ets-family transcription factor, is
required for the development of myeloid and lymphoid lineages, whereas
the transcription factor CCAAT-enhancer binding protein family member
C/EBP Hematopoiesis is the regulated development of
distinct cellular lineages from a common precursor, the hematopoietic
stem cell. Fundamental changes in gene expression result in each cell
type expressing a characteristic complement of genes necessary for its
function. This is achieved through the action of transcriptional regulators with general and restricted expression patterns in the
hematopoietic system.1 The ets domain transcription factor PU.1 is preferentially expressed in myeloid and B
cells.2,3 Inactivation of the PU.1 gene in mice
causes defects in the development of multiple hematopoietic lineages,
including B and T lymphocytes, monocytes, and
granulocytes.4,5 PU.1 regulates the expression of almost
all characterized myeloid genes, including growth factor receptors. In
particular, it directs the monocyte-specific expression of the
macrophage colony-stimulating factor receptor.6,7 PU.1
probably plays an important role at several stages in the differentiation process, and there is evidence that it is active at an
early stage, mediating commitment of multipotential progenitor cells to
the myeloid lineage.8
CCAAT/enhancer-binding protein alpha (C/EBP We propose here that the granulocyte factor C/EBP Cell lines and cell culture
Reporter constructs and expression plasmids
Transient transfections using lipofectamine plus and reporter assays for firefly and Renilla luciferase F9 cells and 293T cells were transfected using lipofectamine plus (Life Technologies) as described by the manufacturer.29 Firefly luciferase activities from the constructs p(PU.1)4TK,23 p(C/EBP)2TK, and pGal4-DBD and Renilla luciferase activity from the internal control plasmid pRL-null were determined 24 hours after the initiation of the transfection protocols using the Dual Luciferase Reporter Assay System (Promega). Firefly luciferase activities were normalized to the Renilla luciferase values of pRL-null. Results are given as mean ± SD of at least 6 independent experiments. The following DNA concentrations of the reporter constructs and expression plasmids were used for lipofectamine plus transfections: 0.1 µg p(PU.1)4TK, p(mutatedPU.1)4TK, p(C/EBP)2TK, and pGal4-DBD and 0.05 µg internal control plasmid pRL-null; 0.1 µg expression plasmids for PU.1, C/EBP , C/EBP mutants, c-Jun, Gal4-PU.1 activation domain,
Gal4-VP16, and Gal4-Tel; the same concentrations of the empty
expression vectors were used as controls, respectively.
Protein interaction assay Protein interaction assays were performed as described previously.23,30 c-Jun and C/EBP were transcribed in
vitro and translated using the TNT reticulocyte lysate system (Promega) and labeled with (35S) methionine (NEN Life Science
Products, Dreieich, Germany). One microliter labeled in
vitro-translated c-Jun or C/EBP was mixed with 1 µg bacterially
expressed GST-PU.1 or with equivalent amounts of GST or
glutathione-agarose beads (Pharmacia, Freiburg, Germany) for 1 hour at
4°C in NETN buffer (20 mM Tris, pH 8.0, 200 mM NaCl, 1 mM EDTA, and
0.5% NP40). GST-PU.1 was recovered using glutathione-agarose beads,
washed 6 times with NETN buffer, and separated by 10% sodium dodecyl
sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) before
autoradiography. The gel was stained with Coomassie brilliant blue
(Gibco) to verify that the protein concentrations of GST-PU.1 and GST
were the same in all lanes.
Coimmunoprecipitation 293T cells were transfected with expression plasmids of PU.1, C/EBP, C/EBP LZ, and C/EBPmBR by using lipofectamine (Gibco BRL). Twenty-four hours after transfection, whole-cell lysates were
incubated with primary antibody diluted 1:1000 and bound to protein A
agarose beads for 90 to 120 minutes on ice in 2% glycerol-0.5%
Nonidet P-40-1 mM EDTA-20 mM Tris-HCl, pH 8-100 mM NaCl-10 mM
MgCl2-0.1 mM ZnSO4. Beads were washed with
prechilled NETN 3 times, and bound proteins were separated on SDS-PAGE
gels and transferred to nitrocellulose membranes for Western blotting. For coimmunoprecipitation of PU.1 and C/EBP, 10 mg PU.1 polyclonal antibody first was coupled to protein A beads. Proteins were detected by enhanced chemiluminescence (Amersham Pharmacia). Primary antibodies used were rabbit anti-PU.1 (sc-352; Santa Cruz Biotechnology, CA) and
rabbit anti-C/EBP polyclonal antibody (sc-9314; Santa Cruz Biotechnology).
RNA extraction and quantitative real-time polymerase chain reaction U937 pPC18 and U937 with Zn-inducible expression of C/EBP
cells were stimulated with 100 µM zinc (ZnSO4) for
different time points, and total RNA was isolated using RNeasy Mini kit
(Qiagen) according to the manufacturer's instructions. One microgram
extracted RNA was subsequently transcribed in a 20 µL cDNA synthesis
reaction using the Omniscript Reverse Transcriptase protocol (Qiagen).
Real-time polymerase chain reaction (PCR) for PU.1 and for the housekeeping gene glucose-6 phosphate dehydrogenase (G6PD) was performed using the Light Cycler Technology (Roche Diagnostics, Mannheim, Germany). For amplification of G6PD, primers were used according to Emig et al.31 PU.1 was amplified using the Light Cycler-Primer set for human Spi-1 (Search-LC, Heidelberg, Germany) following the manufacturer's instructions. G6PD plasmid:pGdBBX, kindly provided by A. Hochhaus, was serially diluted to 10 000 fg, 1000 fg, and 100 fg and was used as a standard curve. The concentration of each sample was calculated automatically by reference to this curve. PU.1 concentration in each sample was relatively quantified by calculating the ratio between PU.1 and the housekeeping gene G6PD. PCR for G6PD was performed using 2 µL Mastermix (Light Cycler FastStart DNA Master SYBR Green l; catalog no. 3 003 230; Roche Diagnostics, Mannheim, Germany), 2 µL cDNA (see above), 4 mM MgCl2, 7.5 µM each primer, and water to a final volume of 20 µL. Amplification occurred in a 3-step cycle procedure initiated by 10-minute denaturation at 95°C to activate the polymerase: 95°C for 0 seconds, annealing at 64°C for 10 seconds, and extension at 72°C for 25 seconds for 35 cycles. Fluorescence of SYBR Green I was measured after each extension step at 530 nm in channel F1. The final PCR cycle was followed by a melting curve analysis to confirm PCR product identity and to differentiate it from nonspecific (eg, primer-dimmer) products. For that, the products were denatured at 95°C, annealed at 65°C, and slowly heated up to 95°C with fluorescence measurement at 0.2°C increments. Some amplified products were checked by electrophoresis on 1% ethidium bromide-stained agarose gels. The estimated size of the amplified fragments matched the calculated size; for PU.1 it was 150 bp, and for G6PD it was 343 bp. Production of retrovirus Mouse PU.1 cDNA followed by internal ribosomal entry site (IRES) nerve growth factor receptor truncated in the cytoplasmic domain (tNGFR) and human C/EBP cDNA followed by IRES
EGFP were subcloned into a retroviral vector, pMSCV, with an LTR
derived from MSCV (pMSCV-PU.1-ires-tNGFR and pMSCV- C/EBP-IRES-EGFP, respectively). To produce virus, plasmid DNA was transfected into 293gp
cells (293 cells containing the gag and pol genes
but lacking an envelope gene) along with 10A1 env expression
plasmid (pCL-10A1)32 by CaPO4 coprecipitation,
and supernatant from the transfected cells was collected to
transduce cells.
Transduction of CD34+ cells Human umbilical cord blood samples were obtained, with informed consent of the parents, from placentas of full-term healthy newborn infants. After the isolation of mononuclear cells from cord blood by density gradient centrifugation with Lymphoprep (Nycomed, Oslo, Norway), CD34+ cells were obtained using magnetic bead separation (MACS CD34+ cell isolation kit; Miltenyi Biotech, Bergisch Gladbach, Germany) according to the manufacturer's instructions. CD34+ cells were prestimulated in Iscoves modified Dulbecco medium (IMDM; Sigma, St Louis, MO) supplemented with 10% FBS, 50 ng/mL stem cell factor, 50 ng/mL thrombopoietin (kindly provided by Kirin, Tokyo, Japan), 50 ng/mL interleukin-6 (IL-6; Peprotech, Rocky Hill, NJ), and 50 ng/mL Flt-3L (Peprotech) for 20 hours. After replating onto recombinant fibronectin fragment-coated culture dishes (Takara Shuzo, Otsu, Japan) containing virus supernatant and 5 µg/mL protamine sulfate (Sigma), cells were centrifuged at 1000g for 30 minutes. Transduction was repeated 3 times with fresh virus supernatant at 12-hour intervals. Sixty hours after the first transduction, NGFR- and EGFP-positive cells were selected by cell sorting on a FACS Vantage (Becton Dickinson, San Jose, CA) and were subjected to subsequent analyses. To detect the expression of tNGFR on the cell surface, cells were stained with mouse anti-human NGFR (Chemicon, Temecula, CA) followed by phycoerythrin (PE)-conjugated rabbit anti-mouse immunoglobulin (DAKO A/S, Glostrup, Denmark).In vitro liquid culture CD34+ cells transduced with either PU.1 or C/EBP
retroviruses or cotransduced with PU.1 and C/EBP retrovirus were
cultured in IMDM supplemented with 10% heat-inactivated FBS and 50 ng/mL stem cell factor, 50 ng/mL G-CSF, 50 ng/mL GM-CSF, and 50 ng/mL IL-3 (Kirin) at 37°C in 5% CO2 atmosphere. On day 10 of
culture, expression of cell surface antigens was analyzed on a FACS
Vantage using PE-conjugated anti-human CD1a, CD15 (Immunotech,
Marseilles, France), CD14, CD80, CD86, and HLA-DR (PharMingen, San
Diego, CA). Cells were also cytocentrifuged onto glass slides and were stained with May-Gruenwald-Giemsa solution (Merck, Darmstadt, Germany)
followed by Giemsa solution (Kanto Chemical Co, Tokyo, Japan).
Immunolocalization U937 cells were cytocentrifuged onto glass slides, fixed with ice-cold acetone for 2 minutes, dried, and rehydrated in phosphate-buffered saline (PBS). Slides were blocked in 10% FCS for 30 minutes at room temperature, washed with PBS, and incubated overnight at 4°C with primary antibodies C/EBP and PU.1 (sc-9314, Santa Cruz Biotechnology; 554268, PharMingen). Cytospins were washed with PBS and
incubated with secondary antibodies Texas red and Cy3 (Dianova GmbH,
Germany) for 45 minutes. The slides were mounted with antifade solution.
C/EBP are present in myeloid progenitor cells,
we asked how cells differentiate into a specific lineage and whether
there is direct interaction or cross-talk between these 2 major
transcription factors. To address this, we used a minimal TK promoter
with 4 PU.1 binding sites only. This minimal promoter was
transactivated 6-fold on transfection of 293T cells with an expression
plasmid of PU.1. The reporter gene expression was determined 24 hours
after transfection. Cotransfection of C/EBP expression plasmid in
the same experiment resulted in a 4-fold decrease of PU.1
transactivation capacity (Figure 1A). As
a control, cotransfection of PU.1 and C/EBP did not affect the
activity of a minimal TK promoter with mutated PU.1 binding sites. In
further control experiments, we transfected 293T cells with a reporter
construct of TK promoter with multimerized C/EBP binding sites and a
C/EBP expression plasmid, transactivating the promoter 11-fold.
There was no change in protein expression of PU.1 on cotransfection
with the C/EBP expression plasmid, as observed by Western blot for
PU.1 from transfected 293T cells (data not shown). To check whether
C/EBP down-regulates transcription factors in a nonspecific fashion,
we transfected 293T cells with expression plasmids of Gal4-VP16,
C/EBP, and the reporter construct pGal4-luc. C/EBP did not
down-regulate the transcriptional activation of Gal4-VP16 in a
nonspecific fashion under the same conditions.
C/EBP and PU.1, we used GST-purified GST-PU.1 and incubated it with in vitro-translated C/EBP. An interaction between PU.1 and C/EBP was observed. This interaction was resistant to the effect of chaotropic agents such as dithiothreitol and a change
in ionic strength during the incubation reaction (Figure 1B). C/EBP
did not bind to GST or beads alone. Given the observed interaction
between C/EBP and PU.1, we examined the intranuclear location of
these proteins. U937 cells were cytocentrifuged and labeled with PU.1
and C/EBP antibodies, respectively. Secondary antibodies were Texas
red for PU.1 and Cy-3 (green) for C/EBP. We observed diffuse nuclear
staining. The overlay shows that both proteins colocalize in the
nucleus (yellow) (Figure 2).
C/EBP
in the same experiment totally blocked the PU.1 transactivation
capacity of the p(PU.1)4TK promoter and the coactivation of PU.1 by
c-Jun (Figure 3A). C/EBP did not down-regulate the transactivation
of Gal4-VP16 in a nonspecific fashion under the same
conditions.
C/EBP inhibits the c-Jun coactivation of PU.1.
To relate these findings to protein-protein interactions between
C/EBP and PU.1, we performed GST pull-down experiments, and
35S-labeled in vitro-translated c-Jun and C/EBP were
incubated with GST-PU.1. We already demonstrated that c-Jun strongly
binds to PU.1,23 and here we show that C/EBP also binds
to PU.1 strongly. When both factors were incubated with PU.1, C/EBP
displaced c-Jun from binding to PU.1 (Figure 3B). We determined
that C/EBP interacted with the  3-4 region of the DNA-binding
domain of PU.1, the same region in which c-Jun interacts with PU.1
(Figure 3C). Incubation of 35S-labeled in vitro-translated
PU.1 with the GST-DNA binding domain of C/EBP showed that C/EBP
interacts with PU.1 through its DNA-binding domain (Figure
3D).
C/EBP , C/EBPLZ, and
C/EBPmBR by using lipofectamine. Whole-cell lysates were immunoprecipitated with either rabbit-immunoglobulin G (IgG) or a
rabbit anti-PU.1 polyclonal antibody. C/EBP was detected by Western
blotting with C/EBP rabbit polyclonal antibody only in PU.1
immunoprecipitates (Figure 4A). In the
control IgG immunoprecipitate, no C/EBP was detected. The blot was
stripped and blotted for PU.1 expression (Figure 4B). Expression of
C/EBP and mutants of C/EBP were investigated by Western blotting
for C/EBP (Figure 4C). C/EBP could not interact with PU.1 when
the leucine zipper in the DNA-binding domain was deleted, suggesting
that C/EBP interacts with PU.1 through its leucine zipper in the
DNA-binding domain.
To address whether C/EBP
C/EBP recruits corepressors to
down-regulate PU.1 transactivation capacity, we transfected F9 cells with the TK promoter containing PU.1-binding sites and expression plasmids of PU.1 and C/EBP. We found that C/EBP blocks the
activity of PU.1 to transactivate the minimal TK promoter with
PU.1-binding sites. Trichostatin A (TSA) has been shown to be an
inhibitor of a class of corepressors. Transcription factor Tel recruits these corepressors and represses the promoter activity of
Gal4-luciferase.33 Addition of TSA releases this
repression as it is seen in the transfection of 293T cells with
Gal4-Tel. On the addition of TSA to the cells, this repression is lost
and the promoter activity is restored. In a similar experiment in which
the transactivation block of PU.1 by C/EBP was seen, the addition of
TSA did not release the repression. These data suggest that repression
of PU.1 activity by C/EBP does not occur through the recruitment of
TSA-sensitive corepressors (Figure
6).
C/EBP blocks the expression of
PU.1 target genes. Because PU.1 is autoregulatory in its
expression,34 PU.1 itself is a target gene of PU.1. We
therefore performed quantitative real-time PCR using real-time Light
Cycler technology (Roche) to determine the expression of PU.1 in the
U937 cell line with Zn-inducible expression of C/EBP.16
To test for variances in the cDNA synthesis step, PU.1 expression was
set in relation to the G6PD housekeeping gene by calculating
the ratios for PU.1/G6PD. C/EBP was expressed maximally after 6 hours of zinc induction (data not shown), and 5 time points of zinc
induction were included to determine PU.1 expression. PU.1 expression
was down-regulated 4-fold after 8 hours. In the control there was only
a minimal change in PU.1 expression on induction with zinc in U937
cells carrying the empty vector pPC18 (Figure
7A). The data are consistent with the
model that the expression of PU.1 is down-regulated after blocking of
PU.1 function by C/EBP. C/EBP blocked the transactivation of PU.1
promoter by PU.1, C/EBP transactivated the promoter alone by 2-fold,
and pGL2 was used as a control (Figure 7B).
C/EBP
in a human bipotential myeloid progenitor cell line induces granulocyte
differentiation and blocks monocyte differentiation.16 On
the other hand, PU.1 has been demonstrated to instruct transformed chicken multipotent hematopoietic progenitors to differentiate along
the myeloid lineage.8 In human CD34+
hematopoietic progenitor cells, however, enforced expression of PU.1
promotes dendritic cell differentiation with characteristics of
Langerhans cells, specific dendritic cells that reside in epidermis (A.I., manuscript in preparation). To investigate the biologic significance of function blocking of PU.1 by C/EBP, we retrovirally expressed PU.1 and C/EBP in human CD34+ hematopoietic
progenitor cells. In contrast to mock control in which granulocytes and
monocytes differentiated (Figure 8A),
single transduction of PU.1 and C/EBP predominantly promoted the
differentiation of CD1a+ dendritic cells (Figure 8B,E-F)
and granulocytes (Figure 8C), respectively. PU.1-transduced cells were
positive for CD1a, HLA-DR, CD80, and CD86 (Figure 8F) suggesting that
PU.1 specifically enhanced dendritic cell expression. In the latter
case of C/EBP transduction, terminal differentiation of neutrophils
was markedly enhanced compared with mock control. Then we coexpressed
PU.1 and C/EBP in CD34+ hematopoietic progenitor cells.
In accordance with our mechanistic data of C/EBP blocking PU.1
transcriptional activity, C/EBP blocked dendritic cell
differentiation by PU.1 and instead induced granulocyte differentiation
(Figure 8D-E).
Transcription factors PU.1 and C/EBP The present work shows that the transcription factor C/EBP PU.1 is autoregulatory in its expression in myeloid
cells.34 We observed that C/EBP It has been shown that PU.1 is essential for the development of
monocytes.37 DeKoter and Singh37 have also
shown that the activation domain of PU.1 is essential to drive the
cells to monocytes. We could observe that C/EBP We have already shown that the enforced expression of C/EBP To prove the biologic meanings of the functional inhibition of PU.1 by
C/EBP
We thank Sheo M. Singh and Abdul Peerzada for valuable discussions. We are grateful to Yoshihiro Shiina for providing us with human cord blood.
Submitted July 19, 2001; accepted March 12, 2002.
Supported by a grant from Deutsche José Carreras Leukaemie Stiftung to V.A.R. (DJCLS-99/NAT-1) and by a Deutsche Forschungsgemeinschaft (DFG) grant to G.B. (Nv 2042/2-1).
The publication costs of this article were defrayed in part by page charge payment. Therefore, and solely to indicate this fact, this article is hereby marked "advertisement" in accordance with 18 U.S.C. section 1734.
Reprints: Gerhard Behre, Department of Medicine III, Ludwig-Maximilians-University Munich, Marchioninistr 15, D-81377 Munich, Germany; e-mail: gerdbehre{at}aol.com.
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 A. FATICA, A. ROSA, F. FAZI, M. BALLARINO, M. MORLANDO, F.G. DE ANGELIS, E. CAFFARELLI, C. NERVI, and I. BOZZONI MicroRNAs and Hematopoietic Differentiation Cold Spring Harb Symp Quant Biol, January 1, 2006; 71(0): 205 - 210. [Abstract] [PDF]
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M. Su, A. K. Bansal, R. Mantovani, and J. Sodek Recruitment of Nuclear Factor Y to the Inverted CCAAT Element (ICE) by c-Jun and E1A Stimulates Basal Transcription of the Bone Sialoprotein Gene in Osteosarcoma Cells J. Biol. Chem., November 18, 2005; 280(46): 38365 - 38375. [Abstract] [Full Text] [PDF]
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T. Shimokawa and C. Ra C/EBP{alpha} functionally and physically interacts with GABP to activate the human myeloid IgA Fc receptor (Fc{alpha}R, CD89) gene promoter Blood, October 1, 2005; 106(7): 2534 - 2542. [Abstract] [Full Text] [PDF]
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B. Jacquelin, T. Kortulewski, P. Vaigot, A. Pawlik, G. Gruel, O. Alibert, P. Soularue, C. Joubert, X. Gidrol, and D. T.-L. Roux Novel pathway for megakaryocyte production after in vivo conditional eradication of integrin {alpha}IIb-expressing cells Blood, September 15, 2005; 106(6): 1965 - 1974. [Abstract] [Full Text] [PDF]
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A. Numata, K. Shimoda, K. Kamezaki, T. Haro, H. Kakumitsu, K. Shide, K. Kato, T. Miyamoto, Y. Yamashita, Y. Oshima, et al. Signal Transducers and Activators of Transcription 3 Augments the Transcriptional Activity of CCAAT/Enhancer-binding Protein {alpha} in Granulocyte Colony-stimulating Factor Signaling Pathway J. Biol. Chem., April 1, 2005; 280(13): 12621 - 12629. [Abstract] [Full Text] [PDF]
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Y. Bakri, S. Sarrazin, U. P. Mayer, S. Tillmanns, C. Nerlov, A. Boned, and M. H. Sieweke Balance of MafB and PU.1 specifies alternative macrophage or dendritic cell fate Blood, April 1, 2005; 105(7): 2707 - 2716. [Abstract] [Full Text] [PDF]
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 T. Ito, C. Nishiyama, M. Nishiyama, H. Matsuda, K. Maeda, Y. Akizawa, R. Tsuboi, K. Okumura, and H. Ogawa Mast Cells Acquire Monocyte-Specific Gene Expression and Monocyte-Like Morphology by Overproduction of PU.1 J. Immunol., January 1, 2005; 174(1): 376 - 383. [Abstract] [Full Text] [PDF]
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M. Witcher, H. Y. Shiu, Q. Guo, and W. H. Miller Jr Combination of retinoic acid and tumor necrosis factor overcomes the maturation block in a variety of retinoic acid-resistant acute promyelocytic leukemia cells Blood, November 15, 2004; 104(10): 3335 - 3342. [Abstract] [Full Text] [PDF]
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F. Takeshita, K. Suzuki, S. Sasaki, N. Ishii, D. M. Klinman, and K. J. Ishii Transcriptional Regulation of the Human TLR9 Gene J. Immunol., August 15, 2004; 173(4): 2552 - 2561. [Abstract] [Full Text] [PDF]
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F. Rosenbauer, K. Wagner, P. Zhang, K.-P. Knobeloch, A. Iwama, and D. G. Tenen pDP4, a novel glycoprotein secreted by mature granulocytes, is regulated by transcription factor PU.1 Blood, June 1, 2004; 103(11): 4294 - 4301. [Abstract] [Full Text] [PDF]
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M. Schwieger, J. Lohler, M. Fischer, U. Herwig, D. G. Tenen, and C. Stocking A dominant-negative mutant of C/EBP{alpha}, associated with acute myeloid leukemias, inhibits differentiation of myeloid and erythroid progenitors of man but not mouse Blood, April 1, 2004; 103(7): 2744 - 2752. [Abstract] [Full Text] [PDF]
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H. Ishii, R. Sen, and M. J. Pazin Combinatorial Control of DNase I-hypersensitive Site Formation and Erasure by Immunoglobulin Heavy Chain Enhancer-binding Proteins J. Biol. Chem., February 20, 2004; 279(8): 7331 - 7338. [Abstract] [Full Text] [PDF]
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S. Ano, R. Pereira, M. Pironin, I. Lesault, C. Milley, I. Lebigot, C. T. Quang, and J. Ghysdael Erythroblast Transformation by FLI-1 Depends upon Its Specific DNA Binding and Transcriptional Activation Properties J. Biol. Chem., January 23, 2004; 279(4): 2993 - 3002. [Abstract] [Full Text] [PDF]
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J.-F. Lambert, M. Liu, G. A. Colvin, M. Dooner, C. I. McAuliffe, P. S. Becker, B. G. Forget, S. M. Weissman, and P. J. Quesenberry Marrow Stem Cells Shift Gene Expression and Engraftment Phenotype with Cell Cycle Transit J. Exp. Med., June 2, 2003; 197(11): 1563 - 1572. [Abstract] [Full Text] [PDF]
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H. Liu, J. R. Keefer, Q.-f. Wang, and A. D. Friedman Reciprocal effects of C/EBPalpha and PKCdelta on JunB expression and monocytic differentiation depend upon the C/EBPalpha basic region Blood, May 15, 2003; 101(10): 3885 - 3892. [Abstract] [Full Text] [PDF]
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R. K. Vangala, M. S. Heiss-Neumann, J. S. Rangatia, S. M. Singh, C. Schoch, D. G. Tenen, W. Hiddemann, and G. Behre The myeloid master regulator transcription factor PU.1 is inactivated by AML1-ETO in t(8;21) myeloid leukemia Blood, January 1, 2003; 101(1): 270 - 277. [Abstract] [Full Text] [PDF]
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J. Rangatia, R. K. Vangala, N. Treiber, P. Zhang, H. Radomska, D. G. Tenen, W. Hiddemann, and G. Behre Downregulation of c-Jun Expression by Transcription Factor C/EBP{alpha} Is Critical for Granulocytic Lineage Commitment Mol. Cell. Biol., December 15, 2002; 22(24): 8681 - 8694. [Abstract] [Full Text] [PDF]
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| Copyright © 2002 by American Society of Hematology Online ISSN: 1528-0020 | |||||||||
inactivates the myeloid master
regulator PU.1: possible role in lineage commitment decisions
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Abstract
Introduction
.
