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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Aneuploidy
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Animals
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Chromosome Segregation / physiology*
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Fibroblasts / cytology
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Gene Targeting / methods
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Genome
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Germ Cells
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Heterochromatin / physiology*
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Histone Methyltransferases
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Histone-Lysine N-Methyltransferase / genetics
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Histone-Lysine N-Methyltransferase / physiology*
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Histones / metabolism
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Hypogonadism
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Lymphoma, B-Cell
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Male
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Mammals
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Meiosis
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Methylation
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Methyltransferases / genetics
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Methyltransferases / physiology*
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Mice
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Mice, Knockout
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Mice, Mutant Strains
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Mutagenesis
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Protein Methyltransferases
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Repressor Proteins / genetics
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Repressor Proteins / physiology*
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Sex Chromosome Aberrations*
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Spermatocytes
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Spermatogenesis / genetics
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Spermatogenesis / physiology
Substances
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Heterochromatin
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Histones
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Repressor Proteins
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Suv39h1 protein, mouse
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Histone Methyltransferases
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Methyltransferases
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Protein Methyltransferases
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Histone-Lysine N-Methyltransferase