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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.

SUBMITTER: Casas-Delucchi CS 

PROVIDER: S-EPMC3072080 | biostudies-other | 2011

REPOSITORIES: biostudies-other

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Histone acetylation controls the inactive X chromosome replication dynamics.

Casas-Delucchi Corella S CS   Brero Alessandro A   Rahn Hans-Peter HP   Solovei Irina I   Wutz Anton A   Cremer Thomas T   Leonhardt Heinrich H   Cardoso M Cristina MC  

Nature communications 20110101


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 perinucleo  ...[more]

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