| Bmi-1 regulates the Ink4a/Arf locus to control pancreatic beta-cell proliferation. | |
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MedLine Citation:
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PMID: 19390085 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The molecular mechanisms that regulate the age-induced increase of p16(INK4a) expression associated with decreased beta-cell proliferation and regeneration are not well understood. We report that in aged islets, derepression of the Ink4a/Arf locus is associated with decreased Bmi-1 binding, loss of H2A ubiquitylation, increased MLL1 recruitment, and a concomitant increase in H3K4 trimethylation. During beta-cell regeneration these histone modifications are reversed resulting in reduced p16(INK4a) expression and increased proliferation. We suggest that PcG and TrxG proteins impart a combinatorial code of histone modifications on the Ink4a/Arf locus to control beta-cell proliferation during aging and regeneration. |
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Authors:
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Sangeeta Dhawan; Shuen-Ing Tschen; Anil Bhushan |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Genes & development Volume: 23 ISSN: 1549-5477 ISO Abbreviation: Genes Dev. Publication Date: 2009 Apr |
Date Detail:
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Created Date: 2009-04-24 Completed Date: 2009-04-27 Revised Date: 2013-05-14 |
Medline Journal Info:
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Nlm Unique ID: 8711660 Medline TA: Genes Dev Country: United States |
Other Details:
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Languages: eng Pagination: 906-11 Citation Subset: IM |
Affiliation:
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Larry L. Hillblom Islet Research Center, Department of Medicine, University of California at Los Angeles, Los Angeles, California 90024, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Aging* Animals Cell Line Cell Proliferation Cyclin-Dependent Kinase Inhibitor p16 / metabolism* Female Gene Expression Profiling Gene Expression Regulation* Glucose Intolerance / metabolism Insulin-Secreting Cells / cytology* Male Mice Mice, Inbred C57BL Mice, Knockout Nuclear Proteins / metabolism* Polycomb Repressive Complex 1 Protein Binding Proto-Oncogene Proteins / metabolism* Repressor Proteins / metabolism* |
| Grant Support | |
ID/Acronym/Agency:
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DK-068763/DK/NIDDK NIH HHS; DK-80996/DK/NIDDK NIH HHS; R01 DK068763/DK/NIDDK NIH HHS; R01 DK080996-04/DK/NIDDK NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Bmi1 protein, mouse; 0/Cyclin-Dependent Kinase Inhibitor p16; 0/Nuclear Proteins; 0/Proto-Oncogene Proteins; 0/Repressor Proteins; EC 6.3.2.19/Polycomb Repressive Complex 1 |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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