title: Phf19 links methylated Lys36 of histone H3 to regulation of Polycomb activity.
abstract: Polycomb-group proteins are transcriptional repressors with essential roles in embryonic development. Polycomb repressive complex 2 (PRC2) contains the methyltransferase activity for Lys27. However, the role of other histone modifications in regulating PRC2 activity is just beginning to be understood. Here we show that direct recognition of methylated histone H3 Lys36 (H3K36me), a mark associated with activation, by the PRC2 subunit Phf19 is required for the full enzymatic activity of the PRC2 complex. Using NMR spectroscopy, we provide structural evidence for this interaction. Furthermore, we show that Phf19 binds to a subset of PRC2 targets in mouse embryonic stem cells and that this is required for their repression and for H3K27me3 deposition. These findings show that the interaction of Phf19 with H3K36me2 and H3K36me3 is essential for PRC2 complex activity and for proper regulation of gene repression in embryonic stem cells.
authors.affiliation: Department of Gene Regulation and Stem Cells, Centre for Genomic Regulation (CRG), Barcelona, Spain.
authors.forename: Cecilia
authors.initials: C
authors.lastname: Ballaré
authors.forename: Martin
authors.initials: M
authors.lastname: Lange
authors.forename: Audrone
authors.initials: A
authors.lastname: Lapinaite
authors.forename: Gloria Mas
authors.initials: GM
authors.lastname: Martin
authors.forename: Lluis
authors.initials: L
authors.lastname: Morey
authors.forename: Gloria
authors.initials: G
authors.lastname: Pascual
authors.forename: Robert
authors.initials: R
authors.lastname: Liefke
authors.forename: Bernd
authors.initials: B
authors.lastname: Simon
authors.forename: Yang
authors.initials: Y
authors.lastname: Shi
authors.forename: Or
authors.initials: O
authors.lastname: Gozani
authors.forename: Teresa
authors.initials: T
authors.lastname: Carlomagno
authors.forename: Salvador Aznar
authors.initials: SA
authors.lastname: Benitah
authors.forename: Luciano
authors.initials: L
authors.lastname: Di Croce
mesh_terms: D002454:Cell Differentiation; D004268:DNA-Binding Proteins; D006657:Histones / Q000378:metabolism*; D006801:Humans; D008239:Lysine / Q000378:metabolism*; D008958:Models, Molecular; D009687:Nuclear Proteins / Q000737:chemistry / Q000378:metabolism*; D014157:Transcription Factors
chemical_list: D004268:DNA-Binding Proteins; D006657:Histones; D009687:Nuclear Proteins; C497703:PHF19 protein, human; D014157:Transcription Factors; D008239:Lysine