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. XCI is usually divided in two phases, the establishment phase when gene silencing is reversible, and maintenance phase when gene silencing becomes irreversible. 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. Among these, Xist recruits proteins of the Polycomb repressive complexes. Whether Xist directly recruits Polycomb repressive complex 2 (PRC2) to the chromatin or this recruitment is the consequence of Xist-mediated changes on the chromatin has been object of intense debate. Recent analysis of Xist interacting proteins and genetic analysis seem to suggest that the recruitment is indirect. 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. 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. More studies are needed to finally address this point.

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