title: RBP2 is an MRG15 complex component and down-regulates intragenic histone H3 lysine 4 methylation.
abstract: MRG15 is a conserved chromodomain protein that associates with histone deacetylases (HDACs) and Tip60-containing histone acetyltransferase (HAT) complexes. Here we further characterize MRG15-containing complexes and show a functional link between MRG15 and histone H3K4 demethylase activity in mammalian cells. MRG15 was predominantly localized to discrete nuclear subdomains enriched for Ser(2)-phosphorylated RNA polymerase II, suggesting it is involved specifically with active transcription. Protein analysis of the MRG15-containing complexes led to the identification of RBP2, a JmjC domain-containing protein. Remarkably, over-expression of RBP2 greatly reduced the H3K4 methylation in culture human cells in vivo, and recombinant RBP2 efficiently removed H3K4 methylation of histone tails in vitro. Knockdown of RBP2 resulted in increased H3K4 methylation levels within transcribed regions of active genes. Our findings demonstrate that RBP2 associated with MRG15 complex to maintain reduced H3K4 methylation at transcribed regions, which may ensure the transcriptional elongation state.
authors.affiliation: Laboratory for Chromatin Dynamics, Center for Developmental Biology, RIKEN, Kobe, Hyogo 650-0047, Japan.
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Hayakawa
authors.forename: Yasuko
authors.initials: Y
authors.lastname: Ohtani
authors.forename: Noriyo
authors.initials: N
authors.lastname: Hayakawa
authors.forename: Kaori
authors.initials: K
authors.lastname: Shinmyozu
authors.forename: Motoki
authors.initials: M
authors.lastname: Saito
authors.forename: Fuyuki
authors.initials: F
authors.lastname: Ishikawa
authors.forename: Jun-ichi
authors.initials: J
authors.lastname: Nakayama
mesh_terms: D002460:Cell Line; D015536:Down-Regulation; D015966:Gene Expression Regulation, Fungal; D011495:Histone-Lysine N-Methyltransferase / Q000737:chemistry / Q000502:physiology*; D006657:Histones / Q000737:chemistry*; D006801:Humans; D008239:Lysine / Q000737:chemistry*; D008745:Methylation; D008954:Models, Biological; D008957:Models, Genetic; D010766:Phosphorylation; D012177:Retinol-Binding Proteins / Q000737:chemistry / Q000502:physiology*; D054840:Retinol-Binding Proteins, Cellular; D012441:Saccharomyces cerevisiae / Q000378:metabolism; D012694:Serine / Q000737:chemistry; D014157:Transcription Factors / Q000737:chemistry / Q000502:physiology*; D014158:Transcription, Genetic
chemical_list: D006657:Histones; C470833:MORF4L1 protein, human; C518459:RBP2 protein, human; D012177:Retinol-Binding Proteins; D054840:Retinol-Binding Proteins, Cellular; D014157:Transcription Factors; D012694:Serine; D011495:Histone-Lysine N-Methyltransferase; D008239:Lysine