SEARCH:   Advanced

Blood, 15 November 2004, Vol. 104, No. 10, pp. 3136-3147. Prepublished online as a Blood First Edition Paper on August 5, 2004; DOI 10.1182/blood-2004-04-1603. This Article Full Text Full Text (PDF) All Versions of this Article: 2004-04-1603v1 104/10/3136    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Welch, J. J. Articles by Weiss, M. J. Search for Related Content PubMed PubMed Citation Articles by Welch, J. J. Articles by Weiss, M. J. Related Collections Gene Expression Genomics Hematopoiesis and Stem Cells Red Cells Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMATOPOIESIS Global regulation of erythroid gene expression by transcription factor GATA-1 John J. Welch, Jason A. Watts, Christopher R. Vakoc, Yu Yao, Hao Wang, Ross C. Hardison, Gerd A. Blobel, Lewis A. Chodosh, and Mitchell J. Weiss From The Children's Hospital of Philadelphia, Division of Hematology, and the University of Pennsylvania, Philadelphia; the Cell and Molecular Biology and Combined Degree Graduate Programs, The University of Pennsylvania School of Medicine, Philadelphia; the Department of Biochemistry and Molecular Biology, Center for Comparative Genomics and Bioinformatics, Huck Institutes of Life Sciences, The Pennsylvania State University, University Park, PA; and the Department of Cancer Biology, Abramson Family Cancer Research Institute, University of Pennsylvania, Philadelphia. Transcription factor GATA-1 is required for erythropoiesis, yet its full actions are unknown. We performed transcriptome analysis of G1E-ER4 cells, a GATA-1–null erythroblast line that undergoes synchronous erythroid maturation when GATA-1 activity is restored. We interrogated more than 9000 transcripts at 6 time points representing the transition from late burst forming unit–erythroid (BFU-E) to basophilic erythroblast stages. Our findings illuminate several new aspects of GATA-1 function. First, the large number of genes responding quickly to restoration of GATA-1 extends the repertoire of its potential targets. Second, many transcripts were rapidly down-regulated, highlighting the importance of GATA-1 in gene repression. Third, up-regulation of some known GATA-1 targets was delayed, suggesting that auxiliary factors are required. For example, induction of the direct GATA-1 target gene major globin was late and, surprisingly, required new protein synthesis. In contrast, the gene encoding Fog1, which cooperates with GATA-1 in globin transcription, was rapidly induced independently of protein synthesis. Guided by bioinformatic analysis, we demonstrated that selected regions of the Fog1 gene exhibit enhancer activity and in vivo occupancy by GATA-1. These findings define a regulatory loop for globin expression and, more generally, demonstrate how transcriptome analysis can be used to generate testable hypotheses regarding transcriptional networks. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: B. K. Singleton, N. M. Burton, C. Green, R. L. Brady, and D. J. Anstee Mutations in EKLF/KLF1 form the molecular basis of the rare blood group In(Lu) phenotype Blood, September 1, 2008; 112(5): 2081 - 2088. [Abstract] [Full Text] [PDF] F. Lohmann and J. J. Bieker Activation of Eklf expression during hematopoiesis by Gata2 and Smad5 prior to erythroid commitment Development, June 15, 2008; 135(12): 2071 - 2082. [Abstract] [Full Text] [PDF] A. J. Woo, T. B. Moran, Y. L. Schindler, S.-K. Choe, N. B. Langer, M. R. Sullivan, Y. Fujiwara, B. H. Paw, and A. B. Cantor Identification of ZBP-89 as a Novel GATA-1-Associated Transcription Factor Involved in Megakaryocytic and Erythroid Development Mol. Cell. Biol., April 15, 2008; 28(8): 2675 - 2689. [Abstract] [Full Text] [PDF] D. J. Steger, M. I. Lefterova, L. Ying, A. J. Stonestrom, M. Schupp, D. Zhuo, A. L. Vakoc, J.-E. Kim, J. Chen, M. A. Lazar, et al. DOT1L/KMT4 Recruitment and H3K79 Methylation Are Ubiquitously Coupled with Gene Transcription in Mammalian Cells Mol. Cell. Biol., April 15, 2008; 28(8): 2825 - 2839. [Abstract] [Full Text] [PDF] A. B. Cantor, H. Iwasaki, Y. Arinobu, T. B. Moran, H. Shigematsu, M. R. Sullivan, K. Akashi, and S. H. Orkin Antagonism of FOG-1 and GATA factors in fate choice for the mast cell lineage J. Exp. Med., March 17, 2008; 205(3): 611 - 624. [Abstract] [Full Text] [PDF] L. C. Dore, J. D. Amigo, C. O. dos Santos, Z. Zhang, X. Gai, J. W. Tobias, D. Yu, A. M. Klein, C. Dorman, W. Wu, et al. A GATA-1-regulated microRNA locus essential for erythropoiesis PNAS, March 4, 2008; 105(9): 3333 - 3338. [Abstract] [Full Text] [PDF] V. G. Sankaran, S. H. Orkin,, and C. R. Walkley Rb intrinsically promotes erythropoiesis by coupling cell cycle exit with mitochondrial biogenesis Genes & Dev., February 15, 2008; 22(4): 463 - 475. [Abstract] [Full Text] [PDF] R. Endersby, I. J. Majewski, L. Winteringham, J. G. Beaumont, A. Samuels, R. Scaife, E. Lim, M. Crossley, S. P. Klinken, and J.-P. Lalonde Hls5 regulated erythroid differentiation by modulating GATA-1 activity Blood, February 15, 2008; 111(4): 1946 - 1950. [Abstract] [Full Text] [PDF] G. D. Gregory, C. R. Vakoc, T. Rozovskaia, X. Zheng, S. Patel, T. Nakamura, E. Canaani, and G. A. Blobel Mammalian ASH1L Is a Histone Methyltransferase That Occupies the Transcribed Region of Active Genes Mol. Cell. Biol., December 15, 2007; 27(24): 8466 - 8479. [Abstract] [Full Text] [PDF] E. C. Torchia, K. Boyd, J. E. Rehg, C. Qu, and S. J. Baker EWS/FLI-1 Induces Rapid Onset of Myeloid/Erythroid Leukemia in Mice Mol. Cell. Biol., November 15, 2007; 27(22): 7918 - 7934. [Abstract] [Full Text] [PDF] L. Gutierrez, T. Nikolic, T. B. van Dijk, H. Hammad, N. Vos, M. Willart, F. Grosveld, S. Philipsen, and B. N. Lambrecht Gata1 regulates dendritic-cell development and survival Blood, September 15, 2007; 110(6): 1933 - 1941. [Abstract] [Full Text] [PDF] Y.-Y. Kuo and Z.-F. Chang GATA-1 and Gfi-1B Interplay To Regulate Bcl-xL Transcription Mol. Cell. Biol., June 15, 2007; 27(12): 4261 - 4272. [Abstract] [Full Text] [PDF] S.-I. Kim, S. J. Bultman, H. Jing, G. A. Blobel, and E. H. Bresnick Dissecting Molecular Steps in Chromatin Domain Activation during Hematopoietic Differentiation Mol. Cell. Biol., June 15, 2007; 27(12): 4551 - 4565. [Abstract] [Full Text] [PDF] R. Ferreira, A. Wai, R. Shimizu, N. Gillemans, R. Rottier, M. von Lindern, K. Ohneda, F. Grosveld, M. Yamamoto, and S. Philipsen Dynamic regulation of Gata factor levels is more important than their identity Blood, June 15, 2007; 109(12): 5481 - 5490. [Abstract] [Full Text] [PDF] K. D. Johnson, M. E. Boyer, J.-A. Kang, A. Wickrema, A. B. Cantor, and E. H. Bresnick Friend of GATA-1-independent transcriptional repression: a novel mode of GATA-1 function Blood, June 15, 2007; 109(12): 5230 - 5233. [Abstract] [Full Text] [PDF] C. R. Vakoc, M. M. Sachdeva, H. Wang, and G. A. Blobel Profile of Histone Lysine Methylation across Transcribed Mammalian Chromatin Mol. Cell. Biol., December 15, 2006; 26(24): 9185 - 9195. [Abstract] [Full Text] [PDF] M. A. Keller, S. Addya, R. Vadigepalli, B. Banini, K. Delgrosso, H. Huang, and S. Surrey Transcriptional regulatory network analysis of developing human erythroid progenitors reveals patterns of coregulation and potential transcriptional regulators Physiol Genomics, December 13, 2006; 28(1): 114 - 128. [Abstract] [Full Text] [PDF] M. Stumpf, C. Waskow, M. Krotschel, D. van Essen, P. Rodriguez, X. Zhang, B. Guyot, R. G. Roeder, and T. Borggrefe The mediator complex functions as a coactivator for GATA-1 in erythropoiesis via subunit Med1/TRAP220 PNAS, December 5, 2006; 103(49): 18504 - 18509. [Abstract] [Full Text] [PDF] H. Wang, Y. Zhang, Y. Cheng, Y. Zhou, D. C. King, J. Taylor, F. Chiaromonte, J. Kasturi, H. Petrykowska, B. Gibb, et al. Experimental validation of predicted mammalian erythroid cis-regulatory modules Genome Res., December 1, 2006; 16(12): 1480 - 1492. [Abstract] [Full Text] [PDF] F. Nakazawa, H. Nagai, M. Shin, and G. Sheng Negative regulation of primitive hematopoiesis by the FGF signaling pathway Blood, November 15, 2006; 108(10): 3335 - 3343. [Abstract] [Full Text] [PDF] K. D. Johnson, S.-I. Kim, and E. H. Bresnick Differential sensitivities of transcription factor target genes underlie cell type-specific gene expression profiles PNAS, October 24, 2006; 103(43): 15939 - 15944. [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] L. Pang, H.-H. Xue, G. Szalai, X. Wang, Y. Wang, D. K. Watson, W. J. Leonard, G. A. Blobel, and M. Poncz Maturation stage-specific regulation of megakaryopoiesis by pointed-domain Ets proteins Blood, October 1, 2006; 108(7): 2198 - 2206. [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] F. Bose, C. Fugazza, M. Casalgrandi, A. Capelli, J. M. Cunningham, Q. Zhao, S. M. Jane, S. Ottolenghi, and A. Ronchi Functional Interaction of CP2 with GATA-1 in the Regulation of Erythroid Promoters Mol. Cell. Biol., May 15, 2006; 26(10): 3942 - 3954. [Abstract] [Full Text] [PDF] D. Hodge, E. Coghill, J. Keys, T. Maguire, B. Hartmann, A. McDowall, M. Weiss, S. Grimmond, and A. Perkins A global role for EKLF in definitive and primitive erythropoiesis Blood, April 15, 2006; 107(8): 3359 - 3370. [Abstract] [Full Text] [PDF] K. Kitajima, J. Zheng, H. Yen, D. Sugiyama, and T. Nakano Multipotential differentiation ability of GATA-1-null erythroid-committed cells. Genes & Dev., March 15, 2006; 20(6): 654 - 659. [Abstract] [Full Text] [PDF] J.-P. Bourquin, A. Subramanian, C. Langebrake, D. Reinhardt, O. Bernard, P. Ballerini, A. Baruchel, H. Cave, N. Dastugue, H. Hasle, et al. Identification of distinct molecular phenotypes in acute megakaryoblastic leukemia by gene expression profiling PNAS, February 28, 2006; 103(9): 3339 - 3344. [Abstract] [Full Text] [PDF] W. Zhao, C. Kitidis, M. D. Fleming, H. F. Lodish, and S. Ghaffari Erythropoietin stimulates phosphorylation and activation of GATA-1 via the PI3-kinase/AKT signaling pathway Blood, February 1, 2006; 107(3): 907 - 915. [Abstract] [Full Text] [PDF] J. Zheng, K. Kitajima, E. Sakai, T. Kimura, N. Minegishi, M. Yamamoto, and T. Nakano Differential effects of GATA-1 on proliferation and differentiation of erythroid lineage cells Blood, January 15, 2006; 107(2): 520 - 527. [Abstract] [Full Text] [PDF] D. L. Stachura, S. T. Chou, and M. J. Weiss Early block to erythromegakaryocytic development conferred by loss of transcription factor GATA-1 Blood, January 1, 2006; 107(1): 87 - 97. [Abstract] [Full Text] [PDF] A. H. Schuh, A. J. Tipping, A. J. Clark, I. Hamlett, B. Guyot, F. J. Iborra, P. Rodriguez, J. Strouboulis, T. Enver, P. Vyas, et al. ETO-2 Associates with SCL in Erythroid Cells and Megakaryocytes and Provides Repressor Functions in Erythropoiesis Mol. Cell. Biol., December 1, 2005; 25(23): 10235 - 10250. [Abstract] [Full Text] [PDF] H. Im, J. A. Grass, K. D. Johnson, S.-I. Kim, M. E. Boyer, A. N. Imbalzano, J. J. Bieker, and E. H. Bresnick Chromatin domain activation via GATA-1 utilization of a small subset of dispersed GATA motifs within a broad chromosomal region PNAS, November 22, 2005; 102(47): 17065 - 17070. [Abstract] [Full Text] [PDF] M. S. Sundrud, S. E. VanCompernolle, K. A. Eger, T. C. Bruno, A. Subramaniam, S. Mummidi, S. K. Ahuja, and D. Unutmaz Transcription factor GATA-1 potently represses the expression of the HIV-1 coreceptor CCR5 in human T cells and dendritic cells Blood, November 15, 2005; 106(10): 3440 - 3448. [Abstract] [Full Text] [PDF] C. Kuhl, A. Atzberger, F. Iborra, B. Nieswandt, C. Porcher, and P. Vyas GATA1-Mediated Megakaryocyte Differentiation and Growth Control Can Be Uncoupled and Mapped to Different Domains in GATA1 Mol. Cell. Biol., October 1, 2005; 25(19): 8592 - 8606. [Abstract] [Full Text] [PDF] H. Belanger, P. Beaulieu, C. Moreau, D. Labuda, T. J. Hudson, and D. Sinnett Functional promoter SNPs in cell cycle checkpoint genes Hum. Mol. Genet., September 15, 2005; 14(18): 2641 - 2648. [Abstract] [Full Text] [PDF] K. Maki, T. Yamagata, T. Asai, I. Yamazaki, H. Oda, H. Hirai, and K. Mitani Dysplastic definitive hematopoiesis in AML1/EVI1 knock-in embryos Blood, September 15, 2005; 106(6): 2147 - 2155. [Abstract] [Full Text] [PDF] V. Munugalavadla, L. C. Dore, B. L. Tan, L. Hong, M. Vishnu, M. J. Weiss, and R. Kapur Repression of c-Kit and Its Downstream Substrates by GATA-1 Inhibits Cell Proliferation during Erythroid Maturation Mol. Cell. Biol., August 1, 2005; 25(15): 6747 - 6759. [Abstract] [Full Text] [PDF] D. C. King, J. Taylor, L. Elnitski, F. Chiaromonte, W. Miller, and R. C. Hardison Evaluation of regulatory potential and conservation scores for detecting cis-regulatory modules in aligned mammalian genome sequences Genome Res., August 1, 2005; 15(8): 1051 - 1060. [Abstract] [Full Text] [PDF] R. Tehranchi, R. Invernizzi, A. Grandien, B. Zhivotovsky, B. Fadeel, A.-M. Forsblom, E. Travaglino, J. Samuelsson, R. Hast, L. Nilsson, et al. Aberrant mitochondrial iron distribution and maturation arrest characterize early erythroid precursors in low-risk myelodysplastic syndromes Blood, July 1, 2005; 106(1): 247 - 253. [Abstract] [Full Text] [PDF] R. Ferreira, K. Ohneda, M. Yamamoto, and S. Philipsen GATA1 Function, a Paradigm for Transcription Factors in Hematopoiesis Mol. Cell. Biol., February 15, 2005; 25(4): 1215 - 1227. [Full Text] [PDF]