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Polycomb Proteins Targeted by a Short Repeat RNA to the Mouse X Chromosome
Open accessAbstract
To equalize X-chromosome dosages between the sexes, the female mammal inactivates one of her two X chromosomes. X-chromosome inactivation (XCI) is initiated by expression of Xist , a 17-kb noncoding RNA (ncRNA) that accumulates on the X in cis. Because interacting factors have not been isolated, the mechanism by which Xist induces silencing remains unknown. We discovered a 1.6-kilobase ncRNA (RepA) within Xist and identified the Polycomb complex, PRC2, as its direct target. PRC2 is initially recruited to the X by RepA RNA, with Ezh2 serving as the RNA binding subunit. The antisense Tsix RNA inhibits this interaction. RepA depletion abolishes full-length Xist induction and trimethylation on lysine 27 of histone H3 of the X. Likewise, PRC2 deficiency compromises Xist up-regulation. Therefore, RepA, together with PRC2, is required for the initiation and spread of XCI. We conclude that a ncRNA cofactor recruits Polycomb complexes to their target locus.
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Cited by
Long non-coding RNAs: insights into functions
Mercer, T. R., Dinger, M. E., & Mattick, J. S. (2009) · Nature Reviews Genetics · doi:10.1038/nrg2521 · Cited by 5,654
Chromatin signature reveals over a thousand highly conserved large non-coding RNAs in mammals
Guttman, M., Amit, I., Garber, M., French, C., Lin, M. F., Feldser, D., Huarte, M., Zuk, O., Carey, B. W., Cassady, J. P., et al. (2009) · Nature · doi:10.1038/nature07672 · Cited by 4,098
Evolution and Functions of Long Noncoding RNAs
Ponting, C. P., Oliver, P. L., & Reik, W. (2009) · Cell · doi:10.1016/j.cell.2009.02.006 · Cited by 4,208
The Polycomb complex PRC2 and its mark in life
Margueron, R., & Reinberg, D. (2011) · Nature · doi:10.1038/nature09784 · Cited by 3,347
CpG islands and the regulation of transcription
Deaton, A. M., & Bird, A. (2011) · Genes & Development · doi:10.1101/gad.2037511 · Cited by 3,187
Metadata
- Authors
- Zhao, J., Sun, B. K., Erwin, J. A., Song, J.-J., & Lee, J. T.
- Venue
- Science
- Published
- 2008-10-31
- Volume
- 322
- Issue
- 5902
- Pages
- 750-756
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W1977943782
- Cited by
- 1,579
- References
- 0
- FWCI
- 43.59
- Type
- journal article
- Language
- en
- Open access
- green
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- Zhao, J., Sun, B. K., Erwin, J. A., Song, J.-J., & Lee, J. T. (2008). Polycomb Proteins Targeted by a Short Repeat RNA to the Mouse X Chromosome. Science. https://doi.org/10.1126/science.1163045
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