title: Dissecting the role of H3K64me3 in mouse pericentromeric heterochromatin.
abstract: To ensure genome stability, pericentromeric regions are compacted in a dense heterochromatic structure through a combination of specific 'epigenetic' factors and modifications. A cascadal pathway is responsible for establishing pericentromeric chromatin involving chromatin modifiers and 'readers', such as H3K9 histone methyltransferases (Suv)39h and heterochromatin protein 1. Here we define how H3K64me3 on the lateral surface of the histone octamer integrates within the heterochromatinization cascade. Our data suggest that enrichment of H3K64me3 at pericentromeric chromatin foci is dependent on H3K9me3 but independent of a number of central factors such as heterochromatin protein 1, DNA methyltransferases and Suv4-20h histone methyltransferases. Our results support a model in which pericentromeric heterochromatin foci are formed along distinct pathways upon H3K9 trimethylation, involving H3K64me3 to potentially stabilize DNA-histone interactions, as well as sequential recruitment of repressive histone tail and DNA modifications. We hence suggest that multiple mechanisms ensure heterochromatin integrity at pericentromeres, with H3K64me3 as an important factor.
authors.affiliation: Max-Planck-Institute of Immunobiology and Epigenetics, 79108 Freiburg, Germany.
authors.forename: Ulrike C
authors.initials: UC
authors.lastname: Lange
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Siebert
authors.forename: Mark
authors.initials: M
authors.lastname: Wossidlo
authors.forename: Thomas
authors.initials: T
authors.lastname: Weiss
authors.forename: Céline
authors.initials: C
authors.lastname: Ziegler-Birling
authors.forename: Jörn
authors.initials: J
authors.lastname: Walter
authors.forename: Maria-Elena
authors.initials: ME
authors.lastname: Torres-Padilla
authors.forename: Sylvain
authors.initials: S
authors.lastname: Daujat
authors.forename: Robert
authors.initials: R
authors.lastname: Schneider
mesh_terms: D000818:Animals; D002503:Centromere / Q000378:metabolism*; D000090266:Chromobox Protein Homolog 5; D002868:Chromosomal Proteins, Non-Histone / Q000378:metabolism; D019175:DNA Methylation / Q000235:genetics; D005455:Fluorescent Antibody Technique; D006570:Heterochromatin / Q000378:metabolism*; D011495:Histone-Lysine N-Methyltransferase / Q000378:metabolism; D006657:Histones / Q000378:metabolism*; D006801:Humans; D008239:Lysine / Q000378:metabolism*; D051379:Mice; D041681:NIH 3T3 Cells; D015053:Zygote / Q000378:metabolism
chemical_list: D002868:Chromosomal Proteins, Non-Histone; D006570:Heterochromatin; D006657:Histones; D000090266:Chromobox Protein Homolog 5; D011495:Histone-Lysine N-Methyltransferase; D008239:Lysine