title: 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.
authors.affiliation: Department of Biochemistry and Biophysics, University of California San Francisco, San Francisco, CA 94143, USA.
authors.forename: Kathrin
authors.initials: K
authors.lastname: Plath
authors.forename: Jia
authors.initials: J
authors.lastname: Fang
authors.forename: Susanna K
authors.initials: SK
authors.lastname: Mlynarczyk-Evans
authors.forename: Ru
authors.initials: R
authors.lastname: Cao
authors.forename: Kathleen A
authors.initials: KA
authors.lastname: Worringer
authors.forename: Hengbin
authors.initials: H
authors.lastname: Wang
authors.forename: Cecile C
authors.initials: CC
authors.lastname: de la Cruz
authors.forename: Arie P
authors.initials: AP
authors.lastname: Otte
authors.forename: Barbara
authors.initials: B
authors.lastname: Panning
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhang
mesh_terms: D000818:Animals; D001755:Blastocyst / Q000378:metabolism / Q000502:physiology*; D002454:Cell Differentiation; D002467:Cell Nucleus / Q000378:metabolism; D002478:Cells, Cultured; D004303:Dosage Compensation, Genetic; D005260:Female; D005455:Fluorescent Antibody Technique; D018392:Genomic Imprinting; D006367:HeLa Cells; D006657:Histones / Q000378:metabolism*; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008239:Lysine / Q000378:metabolism; D008297:Male; D008745:Methylation; D051379:Mice; D009154:Mutation; D063151:Polycomb Repressive Complex 2; D062085:RNA, Long Noncoding; D022661:RNA, Untranslated / Q000235:genetics / Q000378:metabolism; D012097:Repressor Proteins / Q000378:metabolism; D013234:Stem Cells / Q000378:metabolism / Q000502:physiology*; D019076:Transgenes; D014327:Trophoblasts / Q000502:physiology*; D014960:X Chromosome / Q000378:metabolism*
chemical_list: C491488:EED protein, human; C107275:Eed protein, mouse; D006657:Histones; D062085:RNA, Long Noncoding; D022661:RNA, Untranslated; D012097:Repressor Proteins; C077885:XIST non-coding RNA; D063151:Polycomb Repressive Complex 2; D008239:Lysine