Role of Histone H3 Lysine 27 Methylation in X Inactivation

TLDR

Polycomb group protein Eed is involved in imprinted X‑chromosome inactivation in extraembryonic cells, and its homologous Eed‑Ezh2 complex mediates gene silencing via H3‑K27 methylation, implying a potential role for this mark in X‑inactivation. The study shows that the Eed‑Ezh2 complex transiently associates with the inactive X chromosome during initiation of both imprinted and random X inactivation, with H3‑K27 methylation dependent on Xist RNA but not its silencing activity, indicating that this mark is involved in initiation yet insufficient for silencing.

Abstract

The Polycomb group (PcG) protein Eed is implicated in regulation of imprinted X-chromosome inactivation in extraembryonic cells but not of random X inactivation in embryonic cells. The Drosophila homolog of the Eed-Ezh2 PcG protein complex achieves gene silencing through methylation of histone H3 on lysine 27 (H3-K27), which suggests a role for H3-K27 methylation in imprinted X inactivation. Here we demonstrate that transient recruitment of the Eed-Ezh2 complex to the inactive X chromosome (Xi) occurs during initiation of X inactivation in both extraembryonic and embryonic cells and is accompanied by H3-K27 methylation. Recruitment of the complex and methylation on the Xi depend on Xist RNA but are independent of its silencing function. Together, our results suggest a role for Eed-Ezh2–mediated H3-K27 methylation during initiation of both imprinted and random X inactivation and demonstrate that H3-K27 methylation is not sufficient for silencing of the Xi.