title: Direct interrogation of the role of H3K9 in metazoan heterochromatin function.
abstract: A defining feature of heterochromatin is methylation of Lys9 of histone H3 (H3K9me), a binding site for heterochromatin protein 1 (HP1). Although H3K9 methyltransferases and HP1 are necessary for proper heterochromatin structure, the specific contribution of H3K9 to heterochromatin function and animal development is unknown. Using our recently developed platform to engineer histone genes in Drosophila, we generated H3K9R mutant flies, separating the functions of H3K9 and nonhistone substrates of H3K9 methyltransferases. Nucleosome occupancy and HP1a binding at pericentromeric heterochromatin are markedly decreased in H3K9R mutants. Despite these changes in chromosome architecture, a small percentage of H3K9R mutants complete development. Consistent with this result, expression of most protein-coding genes, including those within heterochromatin, is similar between H3K9R and controls. In contrast, H3K9R mutants exhibit increased open chromatin and transcription from piRNA clusters and transposons, resulting in transposon mobilization. Hence, transposon silencing is a major developmental function of H3K9.
authors: Curriculum in Genetics and Molecular Biology, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA;
authors: Taylor J R
authors: TJ
authors: Penke
authors: Curriculum in Genetics and Molecular Biology, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA; Integrative Program for Biological and Genome Sciences, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA; Department of Genetics, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA; Department of Biology, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA;
authors: Daniel J
authors: DJ
authors: McKay
authors: Curriculum in Genetics and Molecular Biology, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA; Department of Biochemistry and Biophysics, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA; Lineberger Comprehensive Cancer Center, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA.
authors: Brian D
authors: BD
authors: Strahl
authors: Curriculum in Genetics and Molecular Biology, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA; Integrative Program for Biological and Genome Sciences, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA; Department of Genetics, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA; Department of Biology, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA; Lineberger Comprehensive Cancer Center, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA.
authors: A Gregory
authors: AG
authors: Matera
authors: Curriculum in Genetics and Molecular Biology, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA; Integrative Program for Biological and Genome Sciences, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA; Department of Genetics, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA; Department of Biology, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA; Lineberger Comprehensive Cancer Center, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA.
authors: Robert J
authors: RJ
authors: Duronio
mesh_terms: D000818:Animals; D000090266:Chromobox Protein Homolog 5; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics / Q000378:metabolism; D002875:Chromosomes / Q000737:chemistry / Q000235:genetics; D004251:DNA Transposable Elements / Q000235:genetics; D029721:Drosophila Proteins / Q000235:genetics* / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000235:genetics* / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D020868:Gene Silencing; D006570:Heterochromatin / Q000235:genetics / Q000378:metabolism*; D011495:Histone-Lysine N-Methyltransferase / Q000378:metabolism; D006657:Histones / Q000378:metabolism*; D009154:Mutation; D009707:Nucleosomes / Q000378:metabolism; D011485:Protein Binding; D034741:RNA, Small Interfering / Q000235:genetics
chemical_list: D002868:Chromosomal Proteins, Non-Histone; D004251:DNA Transposable Elements; D029721:Drosophila Proteins; D006570:Heterochromatin; D006657:Histones; D009707:Nucleosomes; D034741:RNA, Small Interfering; D000090266:Chromobox Protein Homolog 5; D011495:Histone-Lysine N-Methyltransferase
keywords: Drosophila; H3K9; genomics; heterochromatin; heterochromatin protein 1 (HP1); transposon