期刊
CELL CYCLE
卷 9, 期 10, 页码 1972-1980出版社
TAYLOR & FRANCIS INC
DOI: 10.4161/cc.9.10.11602
关键词
p21; GATA-1; transcription; differentiation; erythroid; Sp1; KLF1
类别
资金
- NIH [HL078381, 1F32 HL077242-0102]
- NIH/MSTP [5T32GM07288]
- IGA, Czech Republic [10310-3]
- MSMT, Czech Republic [2B06077]
- National Cancer Institute Cancer Center [2P30CA13330]
Lineage-determination transcription factors coordinate cell differentiation and proliferation by controlling the synthesis of lineage-specific gene products as well as cell cycle regulators. GATA-1 is a master regulator of erythropoiesis. Its role in regulating erythroid-specific genes has been extensively studied, whereas its role in controlling genes that regulate cell proliferation is less understood. Ectopic expression of GATA-1 in erythroleukemia cells releases the block to their differentiation and leads to terminal cell division. An early event in reprogramming the erythroleukemia cells is induction of the cyclin-dependent kinase inhibitor p21. Remarkably, ectopic expression of p21 also induces the erythroleukemia cells to differentiate. We now report that GATA-1 directly regulates transcription of the p21 gene in both erythroleukemia cells and normal erythroid progenitors. Using reporter, electrophoretic mobility shift, and chromatin immunoprecipitation assays, we show that GATA-1 stimulates p21 gene transcription by binding to consensus binding sites in the upstream region of the p21 gene promoter. This activity is also dependent on a binding site for Sp1/KLF-like factors near the transcription start site. Our findings indicate that p21 is a crucial downstream gene target and effector of GATA-1 during red blood cell terminal differentiation.
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