Role of Histone H3 Lysine 27 Methylation in X Inactivation

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.

Silence of the fathers: Early X inactivation

“…(6,7) Histone modifications in preimplantation embryos Xist coating of the X chromosome is followed by the accumulation of the Eed-Ezh2 protein complex and methylation of lysine 27 of histone H3 (H3K27). (16,17) Additional histone modifications associated with the inactive X include hypoacetylation of H3 and H4, hypomethylation of H3K4, methylation of H3K9, and association of macro H2A. (18) These chromatin modifications are thought to contribute to and ensure the maintenance of X inactivation.…”

Dynamic regulation of Polycomb group activity during plant development

“…The role of the latter in recruiting PRC1 has first been reported for X-chromosome inactivation in the mouse [48], but several long ncRNAs have subsequently been identified in mammals and Drosophila to also recruit PRC2 in cis or trans [1,[49][50]. An interaction between PRC2 and ncRNAs has also been postulated in plants [51], but only recently were such RNAs identified at a PRC2 target gene, possibly recruiting PRC2 to the FLC locus (reviewed in [46]).…”

Epigenetics in development

“…First, Xi is decorated with histone methylation marks characteristic of chromatin silencing. The Polycomb group (PcG) HMT, EZH2, associates with Xi and endows it with the silencing mark H3K27me3 (Plath et al, 2003). Xi also acquires the repressive mark H3K9me2, and the activation mark H3K4me2 is underrepresented (Valley et al, 2006).…”