title: Duplication and maintenance of heterochromatin domains.
abstract: To investigate the mechanisms that assure the maintenance of heterochromatin regions, we took advantage of the fact that clusters of heterochromatin DNA replicate late in S phase and are processed in discrete foci with a characteristic nuclear distribution. At the light microscopy level, within these entities, we followed DNA synthesis, histone H4 acetylation, heterochromatin protein 1 (Hp1alpha and -beta), and chromatin assembly factor 1 (CAF-1). During replication, Hp1alpha and -beta domains of concentration are stably maintained, whereas heterochromatin regions are enriched in both CAF-1 and replication-specific acetylated isoforms of histone H4 (H4Ac 5 and 12). We defined a time window of 20 min for the maintenance of this state. Furthermore, treatment with Trichostatin A (TSA), during and after replication, sustains the H4Ac 5 and 12 state in heterochromatin excluding H4Ac 8 and 16. In comparison, early replication foci, at the same level, did not display any specific enrichment in H4Ac 5 and 12. These data emphasize the specific importance for heterochromatin of the replication-associated H4 isoforms. We propose that perpetuation of heterochromatin involves self-maintenance factors, including local concentration of Hp1alpha and -beta, and that a degree of plasticity is provided by the cycle of H4 acetylation/deacetylation assisted by CAF-1.
authors.affiliation: Institut Curie, Research section, UMR 144 et 218 du Centre National de la Recherche Scientifique (CNRS), 75248 Paris cedex 05, France.
authors.forename: A
authors.initials: A
authors.lastname: Taddei
authors.forename: D
authors.initials: D
authors.lastname: Roche
authors.forename: J B
authors.initials: JB
authors.lastname: Sibarita
authors.forename: B M
authors.initials: BM
authors.lastname: Turner
authors.forename: G
authors.initials: G
authors.lastname: Almouzni
mesh_terms: D000107:Acetylation / Q000187:drug effects; D000818:Animals; D002460:Cell Line; D056504:Chromatin Assembly Factor-1; D000090266:Chromobox Protein Homolog 5; D002868:Chromosomal Proteins, Non-Histone / Q000378:metabolism; D004247:DNA / Q000096:biosynthesis / Q000235:genetics; D004261:DNA Replication / Q000235:genetics; D004268:DNA-Binding Proteins / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D006367:HeLa Cells; D006570:Heterochromatin / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D056572:Histone Deacetylase Inhibitors; D006655:Histone Deacetylases / Q000378:metabolism; D006657:Histones / Q000378:metabolism; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology; D051379:Mice; D020033:Protein Isoforms / Q000378:metabolism; D016196:S Phase / Q000235:genetics; D013997:Time Factors
chemical_list: C000715594:CBX5 protein, human; C533593:CHAF1B protein, human; D056504:Chromatin Assembly Factor-1; D002868:Chromosomal Proteins, Non-Histone; D004268:DNA-Binding Proteins; D006570:Heterochromatin; D056572:Histone Deacetylase Inhibitors; D006657:Histones; D006877:Hydroxamic Acids; D020033:Protein Isoforms; D000090266:Chromobox Protein Homolog 5; C012589:trichostatin A; D004247:DNA; D006655:Histone Deacetylases