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: |
|
| 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: |
|
| URI: |
https://repository.cshl.edu/id/eprint/25396 |
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