title: Histone acetylation controls the inactive X chromosome replication dynamics.
abstract: In mammals, dosage compensation between male and female cells is achieved by inactivating one female X chromosome (Xi). Late replication of Xi was proposed to be involved in the maintenance of its silenced state. Here, we show a highly synchronous replication of the Xi within 1 to 2 h during early-mid S-phase by following DNA replication in living mammalian cells with green fluorescent protein-tagged replication proteins. The Xi was replicated before or concomitant with perinuclear or perinucleolar facultative heterochromatin and before constitutive heterochromatin. Ectopic expression of the X-inactive-specific transcript (Xist) gene from an autosome imposed the same synchronous replication pattern. We used mutations and chemical inhibition affecting different epigenetic marks as well as inducible Xist expression and we demonstrate that histone hypoacetylation has a key role in controlling Xi replication. The epigenetically controlled, highly coordinated replication of the Xi is reminiscent of embryonic genome replication in flies and frogs before genome activation and might be a common feature of transcriptionally silent chromatin.
authors.affiliation: Department of Biology, Technische Universität Darmstadt, Darmstadt 64287, Germany.
authors.forename: Corella S
authors.initials: CS
authors.lastname: Casas-Delucchi
authors.forename: Alessandro
authors.initials: A
authors.lastname: Brero
authors.forename: Hans-Peter
authors.initials: HP
authors.lastname: Rahn
authors.forename: Irina
authors.initials: I
authors.lastname: Solovei
authors.forename: Anton
authors.initials: A
authors.lastname: Wutz
authors.forename: Thomas
authors.initials: T
authors.lastname: Cremer
authors.forename: Heinrich
authors.initials: H
authors.lastname: Leonhardt
authors.forename: M Cristina
authors.initials: MC
authors.lastname: Cardoso
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D041321:Chromosomes, Human, X / Q000235:genetics / Q000378:metabolism; D004261:DNA Replication; D005260:Female; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D006570:Heterochromatin / Q000235:genetics / Q000378:metabolism; D006657:Histones / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D014960:X Chromosome / Q000235:genetics* / Q000378:metabolism; D049951:X Chromosome Inactivation
chemical_list: D006570:Heterochromatin; D006657:Histones