Global regulation of erythroid gene expression by transcription factor GATA-1

Welch, J. J., Watts, J. A., Vakoc, C. R., Yao, Y., Wang, H., Hardison, R. C., Blobel, G. A., Chodosh, L. A., Weiss, M. J. (2004) Global regulation of erythroid gene expression by transcription factor GATA-1. Blood, 104 (10). pp. 3136-3147. ISSN 00064971 (ISSN)

Abstract

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 β major globin was late and, surprisingly, required new protein synthesis. In contrast, the gene encoding Fog1, which cooperates with GATA-1 in β 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 β globin expression and, more generally, demonstrate how transcriptome analysis can be used to generate testable hypotheses regarding transcriptional networks. © 2004 by The American Society of Hematology.

Item Type:	Paper
Uncontrolled Keywords:	beta globin globin hemoglobin beta chain transcription factor GATA 1 animal cell article cell maturation controlled study enhancer region erythroblast erythroid cell erythropoiesis fog1 gene gene gene expression regulation gene locus gene repression genetic transcription hematopoiesis mouse nonhuman priority journal protein synthesis regulatory sequence Animals Carrier Proteins Cell Line DNA-Binding Proteins Enhancer Elements genetics Erythroblasts Erythroid-Specific DNA-Binding Factors GATA1 Transcription Factor Gene Expression Profiling Genetic Complementation Test Humans Mice Nuclear Proteins Reproducibility of Results Transcription Factors Transcription, Genetic
Subjects:	bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification bioinformatics > genomics and proteomics > genetics & nucleic acid processing bioinformatics > genomics and proteomics bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > genes, structure and function > gene expression bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > genes, structure and function > gene regulation bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > genes, structure and function > gene regulation bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > genes, structure and function bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > transcription factor
CSHL Authors:	Vakoc, Christopher R.
Communities:	CSHL labs > Vakoc lab
Depositing User:	CSHL Librarian
Date:	2004
Date Deposited:	19 Mar 2012 18:32
Last Modified:	13 Mar 2013 20:38
Related URLs:	Publisher
URI:	https://repository.cshl.edu/id/eprint/25396

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