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- W2048452797 abstract "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-γ to promoters was lost. Depleting HP1-γ 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-γ to direct heterochromatin formation and silencing of proliferation-promoting genes." @default.
- W2048452797 created "2016-06-24" @default.
- W2048452797 creator A5008581102 @default.
- W2048452797 creator A5009561014 @default.
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- W2048452797 creator A5086161254 @default.
- W2048452797 creator A5086942877 @default.
- W2048452797 date "2011-08-08" @default.
- W2048452797 modified "2023-10-13" @default.
- W2048452797 title "Rb and p130 control cell cycle gene silencing to maintain the postmitotic phenotype in cardiac myocytes" @default.
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- W2048452797 doi "https://doi.org/10.1083/jcb.201012049" @default.
- W2048452797 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/3153646" @default.
- W2048452797 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/21825075" @default.
- W2048452797 hasPublicationYear "2011" @default.