title: Loss of the Suv39h histone methyltransferases impairs mammalian heterochromatin and genome stability.
abstract: Histone H3 lysine 9 methylation has been proposed to provide a major "switch" for the functional organization of chromosomal subdomains. Here, we show that the murine Suv39h histone methyltransferases (HMTases) govern H3-K9 methylation at pericentric heterochromatin and induce a specialized histone methylation pattern that differs from the broad H3-K9 methylation present at other chromosomal regions. Suv39h-deficient mice display severely impaired viability and chromosomal instabilities that are associated with an increased tumor risk and perturbed chromosome interactions during male meiosis. These in vivo data assign a crucial role for pericentric H3-K9 methylation in protecting genome stability, and define the Suv39h HMTases as important epigenetic regulators for mammalian development.
authors.affiliation: Research Institute of Molecular Pathology (IMP), Vienna Biocenter, Dr. Bohrgasse 7, A-1030, Vienna, Austria.
authors.forename: A H
authors.initials: AH
authors.lastname: Peters
authors.forename: D
authors.initials: D
authors.lastname: O'Carroll
authors.forename: H
authors.initials: H
authors.lastname: Scherthan
authors.forename: K
authors.initials: K
authors.lastname: Mechtler
authors.forename: S
authors.initials: S
authors.lastname: Sauer
authors.forename: C
authors.initials: C
authors.lastname: Schöfer
authors.forename: K
authors.initials: K
authors.lastname: Weipoltshammer
authors.forename: M
authors.initials: M
authors.lastname: Pagani
authors.forename: M
authors.initials: M
authors.lastname: Lachner
authors.forename: A
authors.initials: A
authors.lastname: Kohlmaier
authors.forename: S
authors.initials: S
authors.lastname: Opravil
authors.forename: M
authors.initials: M
authors.lastname: Doyle
authors.forename: M
authors.initials: M
authors.lastname: Sibilia
authors.forename: T
authors.initials: T
authors.lastname: Jenuwein
mesh_terms: D000782:Aneuploidy; D000818:Animals; D020090:Chromosome Segregation / Q000502:physiology*; D005347:Fibroblasts / Q000166:cytology; D018390:Gene Targeting / Q000379:methods; D016678:Genome; D005854:Germ Cells; D006570:Heterochromatin / Q000502:physiology*; D000076983:Histone Methyltransferases; D011495:Histone-Lysine N-Methyltransferase / Q000235:genetics / Q000502:physiology*; D006657:Histones / Q000378:metabolism; D007006:Hypogonadism; D016393:Lymphoma, B-Cell; D008297:Male; D008322:Mammals; D008540:Meiosis; D008745:Methylation; D008780:Methyltransferases / Q000235:genetics / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D008817:Mice, Mutant Strains; D016296:Mutagenesis; D011496:Protein Methyltransferases; D012097:Repressor Proteins / Q000235:genetics / Q000502:physiology*; D012729:Sex Chromosome Aberrations; D013090:Spermatocytes; D013091:Spermatogenesis / Q000235:genetics / Q000502:physiology
chemical_list: D006570:Heterochromatin; D006657:Histones; D012097:Repressor Proteins; C498700:Suv39h1 protein, mouse; D000076983:Histone Methyltransferases; D008780:Methyltransferases; D011496:Protein Methyltransferases; D011495:Histone-Lysine N-Methyltransferase