GATA-1 directly regulates p21 gene expression during erythroid differentiation

Michael Papetti, Sandeep N. Wontakal, Tomas Stopka, Arthur I. Skoultchi

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1972-1980
Number of pages9
JournalCell Cycle
Volume9
Issue number10
DOIs
StatePublished - May 15 2010

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Leukemia, Erythroblastic, Acute
Gene Expression
Genes
Cell Differentiation
Binding Sites
Cell Proliferation
Cyclin-Dependent Kinase Inhibitor p21
Erythroid Precursor Cells
Chromatin Immunoprecipitation
Erythropoiesis
Transcription Initiation Site
Cell Division
Cell Cycle
Transcription Factors
Erythrocytes
Ectopic Gene Expression

Keywords

  • Differentiation
  • Erythroid
  • GATA-1
  • KLF1
  • p21
  • Sp1
  • Transcription

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology
  • Developmental Biology

Cite this

GATA-1 directly regulates p21 gene expression during erythroid differentiation. / Papetti, Michael; Wontakal, Sandeep N.; Stopka, Tomas; Skoultchi, Arthur I.

In: Cell Cycle, Vol. 9, No. 10, 15.05.2010, p. 1972-1980.

Research output: Contribution to journalArticle

Papetti, Michael ; Wontakal, Sandeep N. ; Stopka, Tomas ; Skoultchi, Arthur I. / GATA-1 directly regulates p21 gene expression during erythroid differentiation. In: Cell Cycle. 2010 ; Vol. 9, No. 10. pp. 1972-1980.
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