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Histone acetylation controls the inactive X chromosome replication dynamics

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Item Type:Article
Title:Histone acetylation controls the inactive X chromosome replication dynamics
Creators Name:Casas-Delucchi, C.S. and Brero, A. and Rahn, H.P. and Solovei, I. and Wutz, A. and Cremer, T. and Leonhardt, H. and Cardoso, M.C.
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.
Keywords:Cultured Cells, DNA Replication, Fibroblasts, Heterochromatin, Histones, Human X Chromosomes, X Chromosome Inactivation, Animals, Mice
Source:Nature Communications
ISSN:2041-1723
Publisher:Nature Publishing Group (U.K.)
Volume:2
Number:1
Page Range:222
Date:March 2011
Official Publication:https://doi.org/10.1038/ncomms1218
PubMed:View item in PubMed

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