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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 Hematopoiesis and Stem Cells Red Cells Gene Expression Genomics 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. 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