ORBi: Jackers Pascale - Ets-dependent regulation of target gene expression during megakaryopoiesis

Reference : Ets-dependent regulation of target gene expression during megakaryopoiesis


	Document type :	Scientific journals : Article
	Discipline(s) :	Human health sciences : Oncology Human health sciences : Hematology Life sciences : Biochemistry, biophysics & molecular biology
	To cite this reference:	http://hdl.handle.net/2268/16385

Title :	Ets-dependent regulation of target gene expression during megakaryopoiesis
Language :	English
Author, co-author :	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 > >]
Publication date :	10-Dec-2004
Journal title :	Journal of Biological Chemistry
Publisher :	American Society for Biochemistry and Molecular Biology
Volume :	279
Issue/season :	50
Pages :	52183-52190
Audience :	International
ISSN :	0021-9258
e-ISSN :	1083-351X
City :	Baltimore
Country :	MD
Keywords :	[en] Base Sequence ; Cell Line ; DNA/genetics ; DNA-Binding Proteins/genetics/metabolism ; Erythroid-Specific DNA-Binding Factors ; GATA1 Transcription Factor ; Gene Expression Regulation ; Genetic Markers ; Humans ; Integrin alpha2 ; Megakaryocytes/metabolism ; Membrane Glycoproteins/genetics ; Neoplasm Proteins/genetics ; Platelet Glycoprotein GPIb-IX Complex/genetics ; Promoter Regions, Genetic ; Proto-Oncogene Protein c-ets-1 ; Proto-Oncogene Protein c-fli-1 ; Proto-Oncogene Proteins/genetics/metabolism ; Proto-Oncogene Proteins c-ets ; Receptors, Cytokine/genetics ; Receptors, Thrombopoietin ; Thrombopoiesis/genetics ; Trans-Activators/genetics/metabolism ; Transcription Factors/genetics/metabolism
Abstract :	[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 units :	Hollings Cancer Center, Medical University of South Carolina, USA
Funders :	Grant of the "NCI National Institute of Health" (PO1 CA78582) Exchange Visitor Program P-1-715
Name of the research project :	"Role of the Ets-1 and Fli-1 transcription factors in cellular differentiation and development"
Target :	Researchers ; Professionals ; Students
Permalink :	http://hdl.handle.net/2268/16385
DOI :	10.1074/jbc.M407489200

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