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

Title: The impact of chromatin modifiers on the timing of locus replication in mouse embryonic stem cells
Authors: Jorgensen, HF
Azuara, V
Amoils, S
Spivakov, M
Terry, A
Nesterova, T
Cobb, BS
Ramsahoye, B
Merkenschlager, M
Fisher, AG
Item Type: Journal Article
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.
Issue Date: 17-Aug-2007
Date of Acceptance: 17-Aug-2007
URI: http://hdl.handle.net/10044/1/71587
DOI: https://doi.org/10.1186/gb-2007-8-8-r169
ISSN: 1474-7596
Publisher: BMC
Journal / Book Title: Genome Biology
Volume: 8
Issue: 8
Copyright Statement: © 2007 Jørgensen et al.; licensee BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Sponsor/Funder: Medical Research Council (MRC)
Funder's Grant Number: PO4050659629
Keywords: Science & Technology
Life Sciences & Biomedicine
Biotechnology & Applied Microbiology
Genetics & Heredity
H3 LYSINE-9 METHYLATION
RIBOSOMAL-RNA GENES
POLYCOMB-GROUP GENE
MLL-MUTANT MICE
HISTONE ACETYLATION
DNA-REPLICATION
PERICENTRIC HETEROCHROMATIN
SATELLITE REPEATS
NEURAL INDUCTION
S-PHASE
Acetylation
Animals
Cell Line
Chromatin
DNA Methylation
DNA Replication
DNA, Satellite
Embryonic Stem Cells
Gene Expression Regulation, Developmental
Histones
Mice
Mutation
S Phase
Cell Line
Chromatin
Animals
Mice
Histones
DNA, Satellite
S Phase
DNA Methylation
DNA Replication
Gene Expression Regulation, Developmental
Acetylation
Mutation
Embryonic Stem Cells
Science & Technology
Life Sciences & Biomedicine
Biotechnology & Applied Microbiology
Genetics & Heredity
H3 LYSINE-9 METHYLATION
RIBOSOMAL-RNA GENES
POLYCOMB-GROUP GENE
MLL-MUTANT MICE
HISTONE ACETYLATION
DNA-REPLICATION
PERICENTRIC HETEROCHROMATIN
SATELLITE REPEATS
NEURAL INDUCTION
S-PHASE
Bioinformatics
05 Environmental Sciences
06 Biological Sciences
08 Information and Computing Sciences
Publication Status: Published
Article Number: R169
Online Publication Date: 2007-08-17
Appears in Collections:Division of Surgery
Clinical Sciences
Molecular Sciences



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