Role of histone H3 lysine 27 methylation in X inactivation.
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.
Plath
Kathrin
K
Department of Biochemistry and Biophysics, University of California San Francisco, San Francisco, CA 94143, USA.
Fang
Jia
J
Mlynarczyk-Evans
Susanna K
SK
Cao
Ru
R
Worringer
Kathleen A
KA
Wang
Hengbin
H
de la Cruz
Cecile C
CC
Otte
Arie P
AP
Panning
Barbara
B
Zhang
Yi
Y
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*
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