Establishment of histone h3 methylation on the inactive X chromosome requires transient recruitment of Eed-Enx1 polycomb group complexes

Jose Silva; Winifred Mak; Ilona Zvetkova; Ruth Appanah; Tatyana B Nesterova; Zoe Webster; Antoine H F M Peters; Thomas Jenuwein; Arie P Otte; Neil Brockdorff

doi:10.1016/s1534-5807(03)00068-6

Establishment of histone h3 methylation on the inactive X chromosome requires transient recruitment of Eed-Enx1 polycomb group complexes

Dev Cell. 2003 Apr;4(4):481-95. doi: 10.1016/s1534-5807(03)00068-6.

Authors

Jose Silva¹, Winifred Mak, Ilona Zvetkova, Ruth Appanah, Tatyana B Nesterova, Zoe Webster, Antoine H F M Peters, Thomas Jenuwein, Arie P Otte, Neil Brockdorff

Affiliation

¹ X Inactivation Group, MRC Clinical Sciences Centre, ICSM, Hammersmith Hospital, Du Cane Road, London W12 0NN, United Kingdom.

PMID: 12689588
DOI: 10.1016/s1534-5807(03)00068-6

Abstract

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Amino Acid Sequence / genetics
Animals
Cell Differentiation / genetics
Cells, Cultured
Chromatin / genetics
Chromatin / metabolism
DNA Methylation
Dosage Compensation, Genetic*
Embryo, Mammalian / embryology*
Female
Fetus
Gene Expression Regulation, Developmental / genetics
Histone Methyltransferases
Histone-Lysine N-Methyltransferase*
Histones / genetics
Histones / metabolism
Lysine / genetics
Lysine / metabolism
Male
Methyltransferases / genetics
Methyltransferases / metabolism*
Mice
Mice, Inbred C57BL
Polycomb Repressive Complex 2
Polycomb-Group Proteins
Protein Methyltransferases
RNA, Long Noncoding
RNA, Untranslated / genetics
RNA, Untranslated / metabolism
Repressor Proteins / genetics
Repressor Proteins / metabolism*
Totipotent Stem Cells / cytology
Totipotent Stem Cells / metabolism*
X Chromosome / genetics*

Substances

Chromatin
EED protein, human
Eed protein, mouse
Histones
Polycomb-Group Proteins
RNA, Long Noncoding
RNA, Untranslated
Repressor Proteins
XIST non-coding RNA
Histone Methyltransferases
Methyltransferases
Protein Methyltransferases
Histone-Lysine N-Methyltransferase
Polycomb Repressive Complex 2
Lysine