title: Partitioning and plasticity of repressive histone methylation states in mammalian chromatin.
abstract: Methylation of position-specific lysine residues in histone N termini is a central modification for regulating epigenetic transitions in chromatin. Each methylatable lysine residue can exist in a mono-, di-, or trimethylated state, thereby extending the indexing potential of this particular modification. Here, we examine all possible methylation states for histone H3 lysine 9 (H3-K9) and lysine 27 (H3-K27) in mammalian chromatin. Using highly specific antibodies together with quantitative mass spectrometry, we demonstrate that pericentric heterochromatin is selectively enriched for H3-K27 monomethylation and H3-K9 trimethylation. This heterochromatic methylation profile is dependent on the Suv39h histone methyltransferases (HMTases) but independent of the euchromatic G9a HMTase. In Suv39h double null cells, pericentric heterochromatin is converted to alternative methylation imprints and accumulates H3-K27 trimethylation and H3-K9 monomethylation. Our data underscore the selective presence of distinct histone lysine methylation states in partitioning chromosomal subdomains but also reveal a surprising plasticity in propagating methylation patterns in eukaryotic chromatin.
authors.affiliation: Research Institute of Molecular Pathology, The Vienna Biocenter, Dr. Bohrgasse 7, A-1030 Vienna, Austria.
authors.forename: Antoine H F M
authors.initials: AH
authors.lastname: Peters
authors.forename: Stefan
authors.initials: S
authors.lastname: Kubicek
authors.forename: Karl
authors.initials: K
authors.lastname: Mechtler
authors.forename: Roderick J
authors.initials: RJ
authors.lastname: O'Sullivan
authors.forename: Alwin A H A
authors.initials: AA
authors.lastname: Derijck
authors.forename: Laura
authors.initials: L
authors.lastname: Perez-Burgos
authors.forename: Alexander
authors.initials: A
authors.lastname: Kohlmaier
authors.forename: Susanne
authors.initials: S
authors.lastname: Opravil
authors.forename: Makoto
authors.initials: M
authors.lastname: Tachibana
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Shinkai
authors.forename: Joost H A
authors.initials: JH
authors.lastname: Martens
authors.forename: Thomas
authors.initials: T
authors.lastname: Jenuwein
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D002843:Chromatin / Q000378:metabolism*; D016678:Genome; D000076983:Histone Methyltransferases; D011495:Histone-Lysine N-Methyltransferase / Q000378:metabolism; D006657:Histones / Q000378:metabolism*; D008239:Lysine / Q000378:metabolism; D013058:Mass Spectrometry; D008745:Methylation; D008780:Methyltransferases / Q000378:metabolism; D051379:Mice; D008969:Molecular Sequence Data; D011496:Protein Methyltransferases; D012097:Repressor Proteins / Q000378:metabolism
chemical_list: D002843:Chromatin; D006657:Histones; D012097:Repressor Proteins; C498700:Suv39h1 protein, mouse; D000076983:Histone Methyltransferases; D008780:Methyltransferases; D011496:Protein Methyltransferases; D011495:Histone-Lysine N-Methyltransferase; D008239:Lysine