The DOI matches its Crossref record; 12 of the 12 references it cites were found in a registry or an index.
Rb and p130 control cell cycle gene silencing to maintain the postmitotic phenotype in cardiac myocytes
Open accessAbstract
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.
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Cites
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Cited by
Puente, B. N., Kimura, W., Muralidhar, S. A., Moon, J., Amatruda, J. F., Phelps, K. L., Grinsfelder, D., Rothermel, B. A., Chen, R., Garcia, J. A., et al. (2014) · Cell · doi:10.1016/j.cell.2014.03.032 · Cited by 909
Meis1 regulates postnatal cardiomyocyte cell cycle arrest
Mahmoud, A. I., Kocabas, F., Muralidhar, S. A., Kimura, W., Koura, A. S., Thet, S., Porrello, E. R., & Sadek, H. A. (2013) · Nature · doi:10.1038/nature12054 · Cited by 559
The long noncoding RNA Chaer defines an epigenetic checkpoint in cardiac hypertrophy
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Self-citationThe microRNA regulatory landscape of MSC-derived exosomes: a systems view
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Metadata
- Authors
- Sdek, P., Zhao, P., Wang, Y., Huang, C.-J., Ko, C. Y., Butler, P. C., Weiss, J. N., & MacLellan, W. R.
- Venue
- Journal of Cell Biology
- Publisher
- Rockefeller University Press
- Published
- 2011-08-08
- Volume
- 194
- Issue
- 3
- Pages
- 407-423
- ISSN
- 0021-9525 (ISSN-L)
- 1540-8140
- OpenAlex
- W2048452797
- Cited by
- 176
- References
- 12
- FWCI
- 4.00
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Sdek, P., Zhao, P., Wang, Y., Huang, C.-J., Ko, C. Y., Butler, P. C., Weiss, J. N., & MacLellan, W. R. (2011). Rb and p130 control cell cycle gene silencing to maintain the postmitotic phenotype in cardiac myocytes. Journal of Cell Biology. https://doi.org/10.1083/jcb.201012049
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