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- W2023455124 endingPage "5042" @default.
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- W2023455124 abstract "ABSTRACT Transcription factor GATA-1 is essential for erythroid and megakaryocytic maturation. GATA-1 mutations are associated with hematopoietic precursor proliferation and leukemogenesis, suggesting a role in cell cycle control. While numerous GATA-1 target genes specifying mature hematopoietic phenotypes have been identified, how GATA-1 regulates proliferation remains unknown. We used a complementation assay based on synchronous inducible rescue of GATA-1 − erythroblasts to show that GATA-1 promotes both erythroid maturation and G 1 cell cycle arrest. Molecular studies combined with microarray transcriptome analysis revealed an extensive GATA-1-regulated program of cell cycle control in which numerous growth inhibitors were upregulated and mitogenic genes were repressed. GATA-1 inhibited expression of cyclin-dependent kinase (Cdk) 6 and cyclin D2 and induced the Cdk inhibitors p18 INK4C and p27 Kip1 with associated inactivation of all G 1 Cdks. These effects were dependent on GATA-1-mediated repression of the c-myc ( Myc ) proto-oncogene. GATA-1 inhibited Myc expression within 3 h, and chromatin immunoprecipitation studies indicated that GATA-1 occupies the Myc promoter in vivo, suggesting a direct mechanism for gene repression. Surprisingly, enforced expression of Myc prevented GATA-1-induced cell cycle arrest but had minimal effects on erythroid maturation. Our results illustrate how GATA-1, a lineage-determining transcription factor, coordinates proliferation arrest with cellular maturation through distinct, interrelated genetic programs." @default.
- W2023455124 created "2016-06-24" @default.
- W2023455124 creator A5012634831 @default.
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- W2023455124 creator A5057289870 @default.
- W2023455124 date "2003-07-01" @default.
- W2023455124 modified "2023-10-02" @default.
- W2023455124 title "GATA-1-Mediated Proliferation Arrest during Erythroid Maturation" @default.
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