| EKLF/KLF1 controls cell cycle entry via direct regulation of E2f2. | |
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MedLine Citation:
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PMID: 19457859 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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Michael R Tallack; Janelle R Keys; Patrick O Humbert; Andrew C Perkins |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2009-05-20 |
Journal Detail:
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Title: The Journal of biological chemistry Volume: 284 ISSN: 1083-351X ISO Abbreviation: J. Biol. Chem. Publication Date: 2009 Jul |
Date Detail:
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Created Date: 2009-07-27 Completed Date: 2009-10-14 Revised Date: 2010-09-27 |
Medline Journal Info:
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Nlm Unique ID: 2985121R Medline TA: J Biol Chem Country: United States |
Other Details:
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Languages: eng Pagination: 20966-74 Citation Subset: IM |
Affiliation:
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Division of Molecular Genetics and Development, Institute for Molecular Bioscience, University of Queensland, Brisbane, 4072, Australia. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Base Sequence Binding Sites Cell Cycle* Conserved Sequence E2F2 Transcription Factor / genetics, metabolism* E2F4 Transcription Factor / genetics, metabolism Enhancer Elements, Genetic / genetics Erythroid Cells / cytology*, metabolism* Erythropoiesis Gene Deletion Gene Expression Regulation Introns / genetics Kruppel-Like Transcription Factors / deficiency, metabolism* Mice Molecular Sequence Data RNA, Messenger / genetics, metabolism Retinoblastoma Protein / metabolism S Phase Transcription Factors / metabolism |
| Chemical | |
Reg. No./Substance:
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0/E2F2 Transcription Factor; 0/E2F4 Transcription Factor; 0/E2f2 protein, mouse; 0/E2f4 protein, mouse; 0/Kruppel-Like Transcription Factors; 0/RNA, Messenger; 0/Retinoblastoma Protein; 0/Transcription Factors; 0/erythroid Kruppel-like factor |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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