The impact of chromatin modifiers on the timing of locus replication in mouse embryonic stem cells.

Abstract:

BACKGROUND:The time of locus replication during S-phase is tightly regulated and correlates with chromatin state. Embryonic stem (ES) cells have an unusual chromatin profile where many developmental regulator genes that are not yet expressed are marked by both active and repressive histone modifications. This poised or bivalent state is also characterized by locus replication in early S-phase in ES cells, while replication timing is delayed in cells with restricted developmental options. RESULTS:Here we used a panel of mutant mouse ES cell lines lacking important chromatin modifiers to dissect the relationship between chromatin structure and replication timing. We show that temporal control of satellite DNA replication is sensitive to loss of a variety of chromatin modifiers, including Mll, Eed, Dnmt1, Suv39h1/h2 and Dicer. The replication times of many single copy loci, including a 5 Mb contiguous region surrounding the Rex1 gene, were retained in chromatin modifier mutant ES cells, although a subset of loci were affected. CONCLUSION:This analysis demonstrates the importance of chromatin modifiers for maintaining correct replication of satellite sequences in pluripotent ES cells and highlights the sensitivity of some single copy loci to the influence of chromatin modifiers. Abundant histone acetylation is shown to correlate well with early replication. Surprisingly, loss of DNA methylation or histone methylation was tolerated by many loci, suggesting that these modifications may be less influential for the timing of euchromatin replication.

journal_name

Genome Biol

journal_title

Genome biology

authors

Jørgensen HF,Azuara V,Amoils S,Spivakov M,Terry A,Nesterova T,Cobb BS,Ramsahoye B,Merkenschlager M,Fisher AG

doi

10.1186/gb-2007-8-8-r169

subject

Has Abstract

pub_date

2007-01-01 00:00:00

pages

R169

issue

8

eissn

1474-7596

issn

1474-760X

pii

gb-2007-8-8-r169

journal_volume

8

pub_type

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