title: Cdyl, a new partner of the inactive X chromosome and potential reader of H3K27me3 and H3K9me2.
abstract: X chromosome inactivation is a remarkable example of chromosome-wide gene silencing and facultative heterochromatin formation. Numerous histone posttranslational modifications, including H3K9me2 and H3K27me3, accompany this process, although our understanding of the enzymes that lay down these marks and the factors that bind to them is still incomplete. Here we identify Cdyl, a chromodomain-containing transcriptional corepressor, as a new chromatin-associated protein partner of the inactive X chromosome (Xi). Using mouse embryonic stem cell lines with mutated histone methyltransferase activities, we show that Cdyl relies on H3K9me2 for its general association with chromatin in vivo. For its association with Xi, Cdyl requires the process of differentiation and the presence of H3K9me2 and H3K27me3, which both become chromosomally enriched following Xist RNA coating. We further show that the removal of the PRC2 component Eed and subsequent loss of H3K27me3 lead to a reduction of both Cdyl and H3K9me2 enrichment on inactive Xi. Finally, we show that Cdyl associates with the H3K9 histone methyltransferase G9a and the MGA protein, both of which are also found on Xi. We propose that the combination of H3K9me2 and H3K27me3 recruits Cdyl to Xi, and this, in turn, may facilitate propagation of the H3K9me2 mark by anchoring G9a.
authors.affiliation: Mammalian Developmental Epigenetics Group, Institut Curie, CNRS UMR 3215, INSERM U934, Paris, France.
authors.forename: M
authors.initials: M
authors.lastname: Escamilla-Del-Arenal
authors.forename: S T
authors.initials: ST
authors.lastname: da Rocha
authors.forename: C G
authors.initials: CG
authors.lastname: Spruijt
authors.forename: O
authors.initials: O
authors.lastname: Masui
authors.forename: O
authors.initials: O
authors.lastname: Renaud
authors.forename: Arne H
authors.initials: AH
authors.lastname: Smits
authors.forename: R
authors.initials: R
authors.lastname: Margueron
authors.forename: M
authors.initials: M
authors.lastname: Vermeulen
authors.forename: E
authors.initials: E
authors.lastname: Heard
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D002467:Cell Nucleus / Q000378:metabolism; D056970:Co-Repressor Proteins; D053595:Embryonic Stem Cells / Q000502:physiology*; D044127:Epigenesis, Genetic; D005260:Female; D018507:Gene Expression Regulation, Developmental; D057809:HEK293 Cells; D051548:Histone Acetyltransferases; D011495:Histone-Lysine N-Methyltransferase / Q000378:metabolism; D006657:Histones / Q000378:metabolism*; D006801:Humans; D006836:Hydro-Lyases; D008745:Methylation; D051379:Mice; D063150:Polycomb Repressive Complex 1 / Q000378:metabolism; D020033:Protein Isoforms / Q000378:metabolism; D011499:Protein Processing, Post-Translational; D055550:Protein Stability; D011506:Proteins / Q000378:metabolism*; D014212:Tretinoin / Q000502:physiology; D014960:X Chromosome / Q000235:genetics / Q000378:metabolism*; D049951:X Chromosome Inactivation
chemical_list: C519505:Cbx7 protein, mouse; D056970:Co-Repressor Proteins; D006657:Histones; D020033:Protein Isoforms; D011506:Proteins; D014212:Tretinoin; C533711:G9a protein, mouse; D011495:Histone-Lysine N-Methyltransferase; D051548:Histone Acetyltransferases; D063150:Polycomb Repressive Complex 1; C485563:Cdyl protein, mouse; D006836:Hydro-Lyases