Gene Set: WELCH_GATA1_TARGETS

Standard name WELCH_GATA1_TARGETS
Systematic name M1407
Brief description Genes up-regulated after GATA1 [GeneID=2623] activation in G1E-ER4 cells (erythroid precursors engineered to express GATA1 upon addition of estradiol [PubChem=5757]).
Full description or 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 beta major globin was late and, surprisingly, required new protein synthesis. In contrast, the gene encoding Fog1, which cooperates with GATA-1 in beta 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 beta globin expression and, more generally, demonstrate how transcriptome analysis can be used to generate testable hypotheses regarding transcriptional networks.
Collection C2: curated gene sets
      CGP: chemical and genetic perturbations
Source publication Pubmed 15297311   Authors: Welch JJ,Watts JA,Vakoc CR,Yao Y,Wang H,Hardison RC,Blobel GA,Chodosh LA,Weiss MJ
Exact source Fig. 2
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Organism Mus musculus
Contributed by Jean-Pierre Bourquin (Dana-Farber Cancer Institute)
Source platform MOUSE_GENE_SYMBOL
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Version history 3.1: First introduced

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