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EKLF/KLF1 controls cell cycle entry via direct regulation of E2f2
- Source :
- The Journal of biological chemistry. 284(31)
- Publication Year :
- 2009
-
Abstract
- Differentiation of erythroid cells requires precise control over the cell cycle to regulate the balance between cell proliferation and differentiation. The zinc finger transcription factor, erythroid Krüppel-like factor (EKLF/KLF1), is essential for proper erythroid cell differentiation and regulates many erythroid genes. Here we show that loss of EKLF leads to aberrant entry into S-phase of the cell cycle during both primitive and definitive erythropoiesis. This cell cycle defect was associated with a significant reduction in the expression levels of E2f2 and E2f4, key factors necessary for the induction of S-phase gene expression and erythropoiesis. We found and validated novel intronic enhancers in both the E2f2 and E2f4 genes, which contain conserved CACC, GATA, and E-BOX elements. The E2f2 enhancer was occupied by EKLF in vivo. Furthermore, we were able to partially restore cell cycle dynamics in EKLF(-/-) fetal liver upon additional genetic depletion of Rb, establishing a genetic causal link between reduced E2f2 and the EKLF cell cycle defect. Finally, we propose direct regulation of the E2f2 enhancer is a generic mechanism by which many KLFs regulate proliferation and differentiation.
- Subjects :
- Molecular Sequence Data
Kruppel-Like Transcription Factors
KLF1
E2F4 Transcription Factor
Biochemistry
Retinoblastoma Protein
S Phase
Mice
E2F2 Transcription Factor
Erythroid Cells
Animals
Erythropoiesis
Transcription, Chromatin, and Epigenetics
RNA, Messenger
Enhancer
Molecular Biology
Transcription factor
E2F4
Conserved Sequence
Binding Sites
biology
Base Sequence
Cell growth
Cell Cycle
Retinoblastoma protein
Cell Biology
Cell cycle
Molecular biology
Introns
Cell biology
Enhancer Elements, Genetic
Gene Expression Regulation
biology.protein
Gene Deletion
Transcription Factors
Subjects
Details
- ISSN :
- 1083351X
- Volume :
- 284
- Issue :
- 31
- Database :
- OpenAIRE
- Journal :
- The Journal of biological chemistry
- Accession number :
- edsair.doi.dedup.....279330397944dbd8ae0f3639f4879b86