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Genes Dev. 2009 Apr 15;23(8):906-11. doi: 10.1101/gad.1742609.

Bmi-1 regulates the Ink4a/Arf locus to control pancreatic beta-cell proliferation.

Author information

1
Larry L. Hillblom Islet Research Center, Department of Medicine, University of California at Los Angeles, Los Angeles, California 90024, USA.

Abstract

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.

PMID:
19390085
PMCID:
PMC2675870
DOI:
10.1101/gad.1742609
[Indexed for MEDLINE]
Free PMC Article
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