Polycomb recruitment 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.

[2] During the establishment phase of X Chromosome Inactivation (XCI), Xist RNA, the master regulator of this process, is monoallelically upregulated[3] and it spreads in cis along the future inactive X (Xi), relocates to the nuclear periphery.

PRC2 binds the A-repeat (RepA) of Xist RNA directly and with very high affinity (dissociation constants of 10-100 nanomolar),[17][18] supporting Xist-mediated recruitment of PRC2 to the X chromosome.

[22][23] For instance, PRC2 recruitment is linked to PRC1-mediated H2A119 ubiquitination in differentiating embryonic stem cells (ESCs).

[26] It is possible that alternative and complementary pathways such as phase separation [27][28] work to establish PRC2 recruitment on the X in different experimental systems and during different stages of development.

One super resolution study showed that Xist and PRC2 do not directly interact (above), while a second study showed that they are tightly and statistically significantly linked.