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PMID: 12356738 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Control of megakaryocyte-specific gene expression by GATA-1 and FOG-1: role of Ets transcription factors.

The EMBO journal ·Vol. 21 ·No. 19 ·2002-10-01 ·Pages 5225-34

Wang X, Crispino JD, Letting DL, Nakazawa M, Poncz M, Blobel GA

Abstract

The transcription factor GATA-1 and its cofactor FOG-1 are essential for the normal development of erythroid cells and megakaryocytes. FOG-1 can stimulate or inhibit GATA-1 activity depending on cell and promoter context. How the GATA-1-FOG-1 complex controls the expression of distinct sets of gene in megakaryocytes and erythroid cells is not understood. Here, we examine the molecular basis for the megakaryocyte-restricted activation of the alphaIIb gene. FOG-1 stimulates GATA-1-dependent alphaIIb gene expression in a manner that requires their direct physical interaction. Transcriptional output by the GATA-1-FOG-1 complex is determined by the hematopoietic Ets protein Fli-1 that binds to an adjacent Ets element. Chromatin immunoprecipitation experiments show that GATA-1, FOG-1 and Fli-1 co-occupy the alphaIIb promoter in vivo. Expression of several additional megakaryocyte-specific genes that bear tandem GATA and Ets elements in their promoters also depends on the physical interaction between GATA-1 and FOG-1. Our studies define a molecular context for transcriptional activation by GATA-1 and FOG-1, and may explain the occurrence of tandem GATA and Ets elements in the promoters of numerous megakaryocyte-expressed genes.

MeSH Terms
3T3 Cells Animals Carrier Proteins/metabolism Cell Differentiation DNA-Binding Proteins/metabolism Erythroid-Specific DNA-Binding Factors GATA1 Transcription Factor Gene Expression Regulation Liver/embryology,physiology Megakaryocytes/physiology Mice Mice, Inbred C57BL Nuclear Proteins/metabolism Promoter Regions, Genetic Protein Binding Proto-Oncogene Proteins/metabolism Proto-Oncogene Proteins c-ets Recombinant Proteins/metabolism Reverse Transcriptase Polymerase Chain Reaction Stem Cells/cytology,physiology Transcription Factors/metabolism Transfection Zinc Fingers
Chemicals
Carrier Proteins DNA-Binding Proteins Erythroid-Specific DNA-Binding Factors GATA1 Transcription Factor Gata1 protein, mouse Nuclear Proteins Proto-Oncogene Proteins Proto-Oncogene Proteins c-ets Recombinant Proteins Transcription Factors Zfpm1 protein, mouse
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Wang Xun
University of Pennsylvania School of Medicine, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.
Crispino John D
Letting Danielle L
Nakazawa Minako
Poncz Mortimer
Blobel Gerd A
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Article Info
Journal
The EMBO journal
Abbr.
EMBO J
ISSN
0261-4189
DOI
10.1093/emboj/cdf527
Published
2002-10-01
Pages
5225-34
Language
English
Region
England
NLM ID
8208664
PMCID
PMC129049
Subset
IM
Grants
NHLBI NIH HHS · P01 HL040387 · United States
NIDDK NIH HHS · R01 DK054937 · United States
NHLBI NIH HHS · P01 HL 40387 · United States
NIDDK NIH HHS · R01 DK 54937 · United States
External Links
PubMed source DOI: 10.1093/emboj/cdf527 PMC Full Text View journal details
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