Document Detail


Bmi-1 regulates the Ink4a/Arf locus to control pancreatic beta-cell proliferation.
MedLine Citation:
PMID:  19390085     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Sangeeta Dhawan; Shuen-Ing Tschen; Anil Bhushan
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Genes & development     Volume:  23     ISSN:  1549-5477     ISO Abbreviation:  Genes Dev.     Publication Date:  2009 Apr 
Date Detail:
Created Date:  2009-04-24     Completed Date:  2009-04-27     Revised Date:  2013-05-14    
Medline Journal Info:
Nlm Unique ID:  8711660     Medline TA:  Genes Dev     Country:  United States    
Other Details:
Languages:  eng     Pagination:  906-11     Citation Subset:  IM    
Affiliation:
Larry L. Hillblom Islet Research Center, Department of Medicine, University of California at Los Angeles, Los Angeles, California 90024, USA.
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MeSH Terms
Descriptor/Qualifier:
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:
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:
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

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