The Recruitment of Chromatin Modifiers by Long Noncoding RNAs: Lessons from PRC2

Overview

Journal RNA

Specialty Molecular Biology

Date 2015 Nov 18

PMID 26574518

Citations 166

Authors

Chen Davidovich

Thomas R Cech

Affiliations

Soon will be listed here.

Abstract

Polycomb repressive complex-2 (PRC2) is a histone methyltransferase required for epigenetic silencing during development and cancer. Among chromatin modifying factors shown to be recruited and regulated by long noncoding RNAs (lncRNAs), PRC2 is one of the most studied. Mammalian PRC2 binds thousands of RNAs in vivo, and it is becoming a model system for the recruitment of chromatin modifying factors by RNA. Yet, well-defined PRC2-binding motifs within target RNAs have been elusive. From the protein side, PRC2 RNA-binding subunits contain no known RNA-binding domains, complicating functional studies. Here we provide a critical review of existing models for the recruitment of PRC2 to chromatin by RNAs. This discussion may also serve researchers who are studying the recruitment of other chromatin modifiers by lncRNAs.

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References

Satijn D, Hamer K, den Blaauwen J, Otte A . The polycomb group protein EED interacts with YY1, and both proteins induce neural tissue in Xenopus embryos. Mol Cell Biol. 2001; 21(4):1360-9. PMC: 99588. DOI: 10.1128/MCB.21.4.1360-1369.2001. View

Nesterova T, Slobodyanyuk S, Elisaphenko E, Shevchenko A, Johnston C, Pavlova M . Characterization of the genomic Xist locus in rodents reveals conservation of overall gene structure and tandem repeats but rapid evolution of unique sequence. Genome Res. 2001; 11(5):833-49. PMC: 311126. DOI: 10.1101/gr.174901. View

Pingoud A, Jeltsch A . Structure and function of type II restriction endonucleases. Nucleic Acids Res. 2001; 29(18):3705-27. PMC: 55916. DOI: 10.1093/nar/29.18.3705. View

OConnell S, Wang L, Robert S, Jones C, Saint R, Jones R . Polycomblike PHD fingers mediate conserved interaction with enhancer of zeste protein. J Biol Chem. 2001; 276(46):43065-73. DOI: 10.1074/jbc.M104294200. View

Chen C, Gherzi R, Ong S, Chan E, Raijmakers R, Pruijn G . AU binding proteins recruit the exosome to degrade ARE-containing mRNAs. Cell. 2001; 107(4):451-64. DOI: 10.1016/s0092-8674(01)00578-5. View

Wutz A, Rasmussen T, Jaenisch R . Chromosomal silencing and localization are mediated by different domains of Xist RNA. Nat Genet. 2002; 30(2):167-74. DOI: 10.1038/ng820. View

Mohr S, Stryker J, Lambowitz A . A DEAD-box protein functions as an ATP-dependent RNA chaperone in group I intron splicing. Cell. 2002; 109(6):769-79. DOI: 10.1016/s0092-8674(02)00771-7. View

Elowitz M, Levine A, Siggia E, Swain P . Stochastic gene expression in a single cell. Science. 2002; 297(5584):1183-6. DOI: 10.1126/science.1070919. View

Swain P, Elowitz M, Siggia E . Intrinsic and extrinsic contributions to stochasticity in gene expression. Proc Natl Acad Sci U S A. 2002; 99(20):12795-800. PMC: 130539. DOI: 10.1073/pnas.162041399. View

10.

Czermin B, Melfi R, McCabe D, Seitz V, Imhof A, Pirrotta V . Drosophila enhancer of Zeste/ESC complexes have a histone H3 methyltransferase activity that marks chromosomal Polycomb sites. Cell. 2002; 111(2):185-96. DOI: 10.1016/s0092-8674(02)00975-3. View

11.

Muller J, Hart C, Francis N, Vargas M, Sengupta A, Wild B . Histone methyltransferase activity of a Drosophila Polycomb group repressor complex. Cell. 2002; 111(2):197-208. DOI: 10.1016/s0092-8674(02)00976-5. View

12.

Kim H, Kang K, Kim J . AEBP2 as a potential targeting protein for Polycomb Repression Complex PRC2. Nucleic Acids Res. 2009; 37(9):2940-50. PMC: 2685092. DOI: 10.1093/nar/gkp149. View

13.

Khalil A, Guttman M, Huarte M, Garber M, Raj A, Rivea Morales D . Many human large intergenic noncoding RNAs associate with chromatin-modifying complexes and affect gene expression. Proc Natl Acad Sci U S A. 2009; 106(28):11667-72. PMC: 2704857. DOI: 10.1073/pnas.0904715106. View

14.

Sing A, Pannell D, Karaiskakis A, Sturgeon K, Djabali M, Ellis J . A vertebrate Polycomb response element governs segmentation of the posterior hindbrain. Cell. 2009; 138(5):885-97. DOI: 10.1016/j.cell.2009.08.020. View

15.

Margueron R, Justin N, Ohno K, Sharpe M, Son J, Drury 3rd W . Role of the polycomb protein EED in the propagation of repressive histone marks. Nature. 2009; 461(7265):762-7. PMC: 3772642. DOI: 10.1038/nature08398. View

16.

Rush M, Appanah R, Lee S, Lam L, Goyal P, Lorincz M . Targeting of EZH2 to a defined genomic site is sufficient for recruitment of Dnmt3a but not de novo DNA methylation. Epigenetics. 2009; 4(6):404-14. DOI: 10.4161/epi.4.6.9392. View

17.

Swiezewski S, Liu F, Magusin A, Dean C . Cold-induced silencing by long antisense transcripts of an Arabidopsis Polycomb target. Nature. 2009; 462(7274):799-802. DOI: 10.1038/nature08618. View

18.

Maenner S, Blaud M, Fouillen L, Savoye A, Marchand V, Dubois A . 2-D structure of the A region of Xist RNA and its implication for PRC2 association. PLoS Biol. 2010; 8(1):e1000276. PMC: 2796953. DOI: 10.1371/journal.pbio.1000276. View

19.

Peng J, Valouev A, Swigut T, Zhang J, Zhao Y, Sidow A . Jarid2/Jumonji coordinates control of PRC2 enzymatic activity and target gene occupancy in pluripotent cells. Cell. 2010; 139(7):1290-302. PMC: 2911953. DOI: 10.1016/j.cell.2009.12.002. View

20.

Shen X, Kim W, Fujiwara Y, Simon M, Liu Y, Mysliwiec M . Jumonji modulates polycomb activity and self-renewal versus differentiation of stem cells. Cell. 2010; 139(7):1303-14. PMC: 2810107. DOI: 10.1016/j.cell.2009.12.003. View