Establishment of histone h3 methylation on the inactive X chromosome requires transient recruitment of Eed-Enx1 polycomb group complexes.
Previous studies have implicated the Eed-Enx1 Polycomb group complex in the maintenance of imprinted X inactivation in the trophectoderm lineage in mouse. Here we show that recruitment of Eed-Enx1 to the inactive X chromosome (Xi) also occurs in random X inactivation in the embryo proper. Localization of Eed-Enx1 complexes to Xi occurs very early, at the onset of Xist expression, but then disappears as differentiation and development progress. This transient localization correlates with the presence of high levels of the complex in totipotent cells and during early differentiation stages. Functional analysis demonstrates that Eed-Enx1 is required to establish methylation of histone H3 at lysine 9 and/or lysine 27 on Xi and that this, in turn, is required to stabilize the Xi chromatin structure.
Silva
Jose
J
X Inactivation Group, MRC Clinical Sciences Centre, ICSM, Hammersmith Hospital, Du Cane Road, London W12 0NN, United Kingdom.
Mak
Winifred
W
Zvetkova
Ilona
I
Appanah
Ruth
R
Nesterova
Tatyana B
TB
Webster
Zoe
Z
Peters
Antoine H F M
AH
Jenuwein
Thomas
T
Otte
Arie P
AP
Brockdorff
Neil
N
D000595:Amino Acid Sequence / Q000235:genetics; D000818:Animals; D002454:Cell Differentiation / Q000235:genetics; D002478:Cells, Cultured; D002843:Chromatin / Q000235:genetics / Q000378:metabolism; D019175:DNA Methylation; D004303:Dosage Compensation, Genetic; D004622:Embryo, Mammalian / Q000196:embryology*; D005260:Female; D005333:Fetus; D018507:Gene Expression Regulation, Developmental / Q000235:genetics; D000076983:Histone Methyltransferases; D011495:Histone-Lysine N-Methyltransferase; D006657:Histones / Q000235:genetics / Q000378:metabolism; D008239:Lysine / Q000235:genetics / Q000378:metabolism; D008297:Male; D008780:Methyltransferases / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D063151:Polycomb Repressive Complex 2; D063146:Polycomb-Group Proteins; D011496:Protein Methyltransferases; D062085:RNA, Long Noncoding; D022661:RNA, Untranslated / Q000235:genetics / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D039901:Totipotent Stem Cells / Q000166:cytology / Q000378:metabolism*; D014960:X Chromosome / Q000235:genetics*
D002843:Chromatin; C491488:EED protein, human; C107275:Eed protein, mouse; D006657:Histones; D063146:Polycomb-Group Proteins; D062085:RNA, Long Noncoding; D022661:RNA, Untranslated; D012097:Repressor Proteins; C077885:XIST non-coding RNA; D000076983:Histone Methyltransferases; D008780:Methyltransferases; D011496:Protein Methyltransferases; D011495:Histone-Lysine N-Methyltransferase; D063151:Polycomb Repressive Complex 2; D008239:Lysine