Reference : Ets-dependent regulation of target gene expression during megakaryopoiesis
Scientific journals : Article
Human health sciences : Oncology
Human health sciences : Hematology
Life sciences : Genetics & genetic processes
Life sciences : Biochemistry, biophysics & molecular biology
Life sciences : Anatomy (cytology, histology, embryology...) & physiology
Ets-dependent regulation of target gene expression during megakaryopoiesis
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 mailto [Medical University of South Carolina > Department of Pathology and Laboratory Medicine and Department of Biochemistry and Molecular Biology > Hollings Cancer Center > >]
Journal of Biological Chemistry
American Society for Biochemistry and Molecular Biology
Yes (verified by ORBi)
[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
[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.
Hollings Cancer Center, Medical University of South Carolina, USA
Grant of the "NCI National Institute of Health" (PO1 CA78582) Exchange Visitor Program P-1-715
"Role of the Ets-1 and Fli-1 transcription factors in cellular differentiation and development"
Researchers ; Professionals ; Students

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