title: Pcl-PRC2 is needed to generate high levels of H3-K27 trimethylation at Polycomb target genes.
abstract: PRC2 is thought to be the histone methyltransferase (HMTase) responsible for H3-K27 trimethylation at Polycomb target genes. Here we report the biochemical purification and characterization of a distinct form of Drosophila PRC2 that contains the Polycomb group protein polycomblike (Pcl). Like PRC2, Pcl-PRC2 is an H3-K27-specific HMTase that mono-, di- and trimethylates H3-K27 in nucleosomes in vitro. Analysis of Drosophila mutants that lack Pcl unexpectedly reveals that Pcl-PRC2 is required to generate high levels of H3-K27 trimethylation at Polycomb target genes but is dispensable for the genome-wide H3-K27 mono- and dimethylation that is generated by PRC2. In Pcl mutants, Polycomb target genes become derepressed even though H3-K27 trimethylation at these genes is only reduced and not abolished, and even though targeting of the Polycomb protein complexes PhoRC and PRC1 to Polycomb response elements is not affected. Pcl-PRC2 is thus the HMTase that generates the high levels of H3-K27 trimethylation in Polycomb target genes that are needed to maintain a Polycomb-repressed chromatin state.
authors.affiliation: Gene Expression Programme, EMBL, Heidelberg, Germany.
authors.forename: Maxim
authors.initials: M
authors.lastname: Nekrasov
authors.forename: Tetyana
authors.initials: T
authors.lastname: Klymenko
authors.forename: Sven
authors.initials: S
authors.lastname: Fraterman
authors.forename: Bernadett
authors.initials: B
authors.lastname: Papp
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Oktaba
authors.forename: Thomas
authors.initials: T
authors.lastname: Köcher
authors.forename: Adrian
authors.initials: A
authors.lastname: Cohen
authors.forename: Hendrik G
authors.initials: HG
authors.lastname: Stunnenberg
authors.forename: Matthias
authors.initials: M
authors.lastname: Wilm
authors.forename: Jürg
authors.initials: J
authors.lastname: Müller
mesh_terms: D000818:Animals; D002457:Cell Extracts; D029721:Drosophila Proteins / Q000235:genetics* / Q000302:isolation & purification / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000196:embryology / Q000201:enzymology*; D004625:Embryo, Nonmammalian / Q000166:cytology / Q000378:metabolism; D017344:Genes, Insect / Q000235:genetics*; D000076983:Histone Methyltransferases; D011495:Histone-Lysine N-Methyltransferase / Q000235:genetics* / Q000302:isolation & purification / Q000378:metabolism*; D006657:Histones / Q000378:metabolism*; D008239:Lysine / Q000378:metabolism*; D008745:Methylation; D063146:Polycomb-Group Proteins; D011496:Protein Methyltransferases; D012097:Repressor Proteins / Q000235:genetics* / Q000378:metabolism; D013379:Substrate Specificity
chemical_list: D002457:Cell Extracts; D029721:Drosophila Proteins; D006657:Histones; D063146:Polycomb-Group Proteins; D012097:Repressor Proteins; D000076983:Histone Methyltransferases; D011496:Protein Methyltransferases; D011495:Histone-Lysine N-Methyltransferase; C524066:PRC2 protein, Drosophila; D008239:Lysine