| First Author | Sdek P | Year | 2011 |
| Journal | J Cell Biol | Volume | 194 |
| Issue | 3 | Pages | 407-23 |
| PubMed ID | 21825075 | Mgi Jnum | J:176968 |
| Mgi Id | MGI:5293252 | Doi | 10.1083/jcb.201012049 |
| Citation | Sdek P, et al. (2011) Rb and p130 control cell cycle gene silencing to maintain the postmitotic phenotype in cardiac myocytes. J Cell Biol 194(3):407-23 |
| abstractText | The mammalian heart loses its regenerative potential soon after birth. Adult cardiac myocytes (ACMs) permanently exit the cell cycle, and E2F-dependent genes are stably silenced, although the underlying mechanism is unclear. Heterochromatin, which silences genes in many biological contexts, accumulates with cardiac differentiation. H3K9me3, a histone methylation characteristic of heterochromatin, also increases in ACMs and at E2F-dependent promoters. We hypothesize that genes relevant for cardiac proliferation are targeted to heterochromatin by retinoblastoma (Rb) family members interacting with E2F transcription factors and recruiting heterochromatin protein 1 (HP1) proteins. To test this hypothesis, we created cardiac-specific Rb and p130 inducible double knockout (IDKO) mice. IDKO ACMs showed a decrease in total heterochromatin, and cell cycle genes were derepressed, leading to proliferation of ACMs. Although Rb/p130 deficiency had no effect on total H3K9me3 levels, recruitment of HP1-gamma to promoters was lost. Depleting HP1-gamma up-regulated proliferation-promoting genes in ACMs. Thus, Rb and p130 have overlapping roles in maintaining the postmitotic state of ACMs through their interaction with HP1-gamma to direct heterochromatin formation and silencing of proliferation-promoting genes. |
