Polycomb recruitment in X chromosome inactivation

Recruitment of Polycomb proteins in X chromosome Inactivation

X chromosome inactivation (XCI) is the phenomenon that has been selected during the evolution to balance X-linked gene dosage between XX females and XY males.[1] XCI is usually divided in two phases, the establishment phase when gene silencing is reversible, and maintenance phase when gene silencing becomes irreversible.[2] During the establishment phase of X Chromosome Inactivation (XCI), Xist RNA, the master regulator of this process, spreads in cis along the future inactive X (Xi) and recruits repressive chromatin-remodelling complexes.[3] Among these, Xist recruits proteins of the Polycomb repressive complexes.[4][5] Whether Xist directly recruits Polycomb repressive complex 2 (PRC2) to the chromatin[6] or this recruitment is the consequence of Xist-mediated changes on the chromatin has been object of intense debate.[7] Recent analysis of Xist interacting proteins [8][9][10] and genetic analysis seem to suggest that the recruitment is indirect.[11][12] Indeed no PRC2 proteins were found by mass spectrometry analysis of Xist-interacting proteins or by loss of function screens. This evidence supports the super resolution microscopy analysis showing that Xist and PRC2 are spatially separated.[13] It is possible that PRC2 is recruited to the chromatin via an adaptor protein or as a consequence of histone deacethylation and RNA pol II exclusion or via PRC1 recruitment.[14][15] More studies are needed to finally address this point.

Xist and PRC2 do not directly interact

References

  1. ↑ Nora, EP; Heard, E (25 November 2009). "X chromosome inactivation: when dosage counts.". Cell. 139 (5): 865–7. doi:10.1016/j.cell.2009.11.009. PMID 19945374.
  2. ↑ Wutz, A; Jaenisch, R (April 2000). "A shift from reversible to irreversible X inactivation is triggered during ES cell differentiation.". Molecular Cell. 5 (4): 695–705. doi:10.1016/s1097-2765(00)80248-8. PMID 10882105.
  3. ↑ Chow, J; Heard, E (June 2009). "X inactivation and the complexities of silencing a sex chromosome.". Current opinion in cell biology. 21 (3): 359–66. doi:10.1016/j.ceb.2009.04.012. PMID 19477626.
  4. ↑ de Napoles, Mariana; Mermoud, Jacqueline E.; Wakao, Rika; Tang, Y. Amy; Endoh, Mitusuhiro; Appanah, Ruth; Nesterova, Tatyana B.; Silva, Jose; Otte, Arie P.; Vidal, Miguel; Koseki, Haruhiko; Brockdorff, Neil (1 November 2004). "Polycomb group proteins Ring1A/B link ubiquitylation of histone H2A to heritable gene silencing and X inactivation". Developmental Cell. 7 (5): 663–676. doi:10.1016/j.devcel.2004.10.005. ISSN 1534-5807. PMID 15525528.
  5. ↑ Plath, Kathrin; Fang, Jia; Mlynarczyk-Evans, Susanna K.; Cao, Ru; Worringer, Kathleen A.; Wang, Hengbin; de la Cruz, Cecile C.; Otte, Arie P.; Panning, Barbara; Zhang, Yi (4 April 2003). "Role of histone H3 lysine 27 methylation in X inactivation". Science. 300 (5616): 131–135. doi:10.1126/science.1084274. ISSN 1095-9203. PMID 12649488.
  6. ↑ Zhao, J; Sun, BK; Erwin, JA; Song, JJ; Lee, JT (31 October 2008). "Polycomb proteins targeted by a short repeat RNA to the mouse X chromosome.". Science. 322 (5902): 750–6. doi:10.1126/science.1163045. PMC 2748911Freely accessible. PMID 18974356.
  7. ↑ Cerase, A; Smeets, D; Tang, YA; Gdula, M; Kraus, F; Spivakov, M; Moindrot, B; Leleu, M; Tattermusch, A; Demmerle, J; Nesterova, TB; Green, C; Otte, AP; Schermelleh, L; Brockdorff, N (11 February 2014). "Spatial separation of Xist RNA and polycomb proteins revealed by superresolution microscopy.". Proceedings of the National Academy of Sciences of the United States of America. 111 (6): 2235–40. doi:10.1073/pnas.1312951111. PMC 3926064Freely accessible. PMID 24469834.
  8. ↑ Chu, C; Zhang, QC; da Rocha, ST; Flynn, RA; Bharadwaj, M; Calabrese, JM; Magnuson, T; Heard, E; Chang, HY (9 April 2015). "Systematic discovery of Xist RNA binding proteins.". Cell. 161 (2): 404–16. doi:10.1016/j.cell.2015.03.025. PMC 4425988Freely accessible. PMID 25843628.
  9. ↑ Minajigi, A; Froberg, JE; Wei, C; Sunwoo, H; Kesner, B; Colognori, D; Lessing, D; Payer, B; Boukhali, M; Haas, W; Lee, JT (17 July 2015). "Chromosomes. A comprehensive Xist interactome reveals cohesin repulsion and an RNA-directed chromosome conformation.". Science. 349 (6245). doi:10.1126/science.aab2276. PMC 4845908Freely accessible. PMID 26089354.
  10. ↑ McHugh, CA; Chen, CK; Chow, A; Surka, CF; Tran, C; McDonel, P; Pandya-Jones, A; Blanco, M; Burghard, C; Moradian, A; Sweredoski, MJ; Shishkin, AA; Su, J; Lander, ES; Hess, S; Plath, K; Guttman, M (14 May 2015). "The Xist lncRNA interacts directly with SHARP to silence transcription through HDAC3.". Nature. 521 (7551): 232–6. doi:10.1038/nature14443. PMC 4516396Freely accessible. PMID 25915022.
  11. ↑ Moindrot, B; Cerase, A; Coker, H; Masui, O; Grijzenhout, A; Pintacuda, G; Schermelleh, L; Nesterova, TB; Brockdorff, N (28 July 2015). "A Pooled shRNA Screen Identifies Rbm15, Spen, and Wtap as Factors Required for Xist RNA-Mediated Silencing.". Cell reports. 12 (4): 562–72. doi:10.1016/j.celrep.2015.06.053. PMC 4534822Freely accessible. PMID 26190105.
  12. ↑ Monfort, A; Di Minin, G; Postlmayr, A; Freimann, R; Arieti, F; Thore, S; Wutz, A (28 July 2015). "Identification of Spen as a Crucial Factor for Xist Function through Forward Genetic Screening in Haploid Embryonic Stem Cells.". Cell reports. 12 (4): 554–61. doi:10.1016/j.celrep.2015.06.067. PMC 4530576Freely accessible. PMID 26190100.
  13. ↑ Cerase, A; Pintacuda, G; Tattermusch, A; Avner, P (15 August 2015). "Xist localization and function: new insights from multiple levels.". Genome Biology. 16: 166. doi:10.1186/s13059-015-0733-y. PMC 4539689Freely accessible. PMID 26282267.
  14. ↑ Pintacuda, G; Cerase, A (October 2015). "X Inactivation Lessons from Differentiating Mouse Embryonic Stem Cells.". Stem cell reviews. 11 (5): 699–705. doi:10.1007/s12015-015-9597-5. PMC 4561061Freely accessible. PMID 26198263.
  15. ↑ Pinter, SF (9 April 2016). "A Tale of Two Cities: How Xist and its partners localize to and silence the bicompartmental X.". Seminars in cell & developmental biology. 56: 19–34. doi:10.1016/j.semcdb.2016.03.023. PMID 27072488.
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