[en] Megakaryopoiesis is the process by which hematopoietic stem cells in the bone marrow differentiate into mature megakaryocytes. The expression of megakaryocytic genes during megakaryopoiesis is controlled by specific transcription factors. Fli-1 and GATA-1 transcription factors are required for development of megakaryocytes and promoter analysis has defined in vitro functional binding sites for these factors in several megakaryocytic genes, including GPIIb, GPIX, and C-MPL. Herein, we utilize chromatin immunoprecipitation to examine the presence of Ets-1, Fli-1, and GATA-1 on these promoters in vivo. Fli-1 and Ets-1 occupy the promoters of GPIIb, GPIX, and C-MPL genes in both Meg-01 and CMK11-5 cells. Whereas GPIIb is expressed in both Meg-01 and CMK11-5 cells, GPIX and C-MPL are only expressed in the more differentiated CMK11-5 cells. Thus, in vivo occupancy by an Ets factor is not sufficient to promote transcription of some megakaryocytic genes. GATA-1 and Fli-1 are both expressed in CMK11-5 cells and co-occupy the GPIX and C-MPL promoters. Transcription of all three megakaryocytic genes is correlated with the presence of acetylated histone H3 and phosphorylated RNA polymerase II on their promoters. We also show that exogenous expression of GATA-1 in Meg-01 cells leads to the expression of endogenous c-mpl and gpIX mRNA. Whereas GPIIb, GPIX, and C-MPL are direct target genes for Fli-1, both Fli-1 and GATA-1 are required for formation of an active transcriptional complex on the C-MPL and GPIX promoters in vivo. In contrast, GPIIb expression appears to be independent of GATA-1 in Meg-01 cells.
Research Center/Unit :
Hollings Cancer Center, Medical University of South Carolina, USA
Jackers, Pascale ; Medical University of South Carolina > Department of Biochemistry and Molecular Biology > Hollings Cancer Center
Szalai, Gabor; Medical University of South Carolina > Department of Biochemistry and Molecular Biology > Hollings Cancer Center
Moussa, Omar; Medical University of South Carolina > Department of Biochemistry and Molecular Biology > Hollings Cancer Center
Watson, Dennis K; Medical University of South Carolina > Department of Pathology and Laboratory Medicine and Department of Biochemistry and Molecular Biology > Hollings Cancer Center
Language :
English
Title :
Ets-dependent regulation of target gene expression during megakaryopoiesis
Publication date :
10 December 2004
Journal title :
Journal of Biological Chemistry
ISSN :
0021-9258
eISSN :
1083-351X
Publisher :
American Society for Biochemistry and Molecular Biology, Baltimore, United States - Maryland
Volume :
279
Issue :
50
Pages :
52183-52190
Peer reviewed :
Peer Reviewed verified by ORBi
Name of the research project :
"Role of the Ets-1 and Fli-1 transcription factors in cellular differentiation and development"
Funders :
Grant of the "NCI National Institute of Health" (PO1 CA78582) Exchange Visitor Program P-1-715
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