title: Higher-order structure in pericentric heterochromatin involves a distinct pattern of histone modification and an RNA component.
abstract: Post-translational modification of histone tails is thought to modulate higher-order chromatin structure. Combinations of modifications including acetylation, phosphorylation and methylation have been proposed to provide marks recognized by specific proteins. This is exemplified, in both mammalian cells and fission yeast, by transcriptionally silent constitutive pericentric heterochromatin. Such heterochromatin contains histones that are generally hypoacetylated and methylated by Suv39h methyltransferases at lysine 9 of histone H3 (H3-K9). Each of these modification states has been implicated in the maintenance of HP1 protein-binding at pericentric heterochromatin, in transcriptional silencing and in centromere function. In particular, H3-K9 methylation is thought to provide a marking system for the establishment and maintenance of stably repressed regions and heterochromatin subdomains. To address the question of how these two types of modifications, as well as other unidentified parameters, function to maintain pericentric heterochromatin, we used a combination of histone deacetylase inhibitors, RNAse treatments and an antibody raised against methylated branched H3-K9 peptides. Our results show that both H3-K9 acetylation and methylation can occur on independent sets of H3 molecules in pericentric heterochromatin. In addition, we identify an RNA- and histone modification-dependent structure that brings methylated H3-K9 tails together in a specific configuration required for the accumulation of HP1 proteins in these domains.
authors.affiliation: Institut Curie, Research section, UMR 218 du CNRS, 26 rue d'Ulm, 75248 Paris cedex 05, France.
authors.forename: Christèle
authors.initials: C
authors.lastname: Maison
authors.forename: Delphine
authors.initials: D
authors.lastname: Bailly
authors.forename: Antoine H F M
authors.initials: AH
authors.lastname: Peters
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Quivy
authors.forename: Danièle
authors.initials: D
authors.lastname: Roche
authors.forename: Angela
authors.initials: A
authors.lastname: Taddei
authors.forename: Monika
authors.initials: M
authors.lastname: Lachner
authors.forename: Thomas
authors.initials: T
authors.lastname: Jenuwein
authors.forename: Geneviève
authors.initials: G
authors.lastname: Almouzni
mesh_terms: D005455:Fluorescent Antibody Technique; D006570:Heterochromatin / Q000737:chemistry / Q000378:metabolism*; D006657:Histones / Q000378:metabolism*; D011487:Protein Conformation; D012313:RNA / Q000737:chemistry / Q000378:metabolism*
chemical_list: D006570:Heterochromatin; D006657:Histones; D012313:RNA