| First Author | Dhawan S | Year | 2009 |
| Journal | Genes Dev | Volume | 23 |
| Issue | 8 | Pages | 906-11 |
| PubMed ID | 19390085 | Mgi Jnum | J:147943 |
| Mgi Id | MGI:3843079 | Doi | 10.1101/gad.1742609 |
| Citation | Dhawan S, et al. (2009) Bmi-1 regulates the Ink4a/Arf locus to control pancreatic beta-cell proliferation. Genes Dev 23(8):906-11 |
| abstractText | 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. |
