Differences in the epigenetic and reprogramming properties of pluripotent and extra-embryonic stem cells implicate chromatin remodelling as an important early event in the developing mouse embryo

Title: Differences in the epigenetic and reprogramming properties of pluripotent and extra-embryonic stem cells implicate chromatin remodelling as an important early event in the developing mouse embryo
Authors: Santos, J
Pereira, CF
Di-Gregorio, A
Spruce, T
Alder, O
Rodriguez, T
Azuara, V
Merkenschlager, M
Fisher, AG
Item Type: Journal Article
Abstract: Background During early mouse development, two extra-embryonic lineages form alongside the future embryo: the trophectoderm (TE) and the primitive endoderm (PrE). Epigenetic changes known to take place during these early stages include changes in DNA methylation and modified histones, as well as dynamic changes in gene expression. Results In order to understand the role and extent of chromatin-based changes for lineage commitment within the embryo, we examined the epigenetic profiles of mouse embryonic stem (ES), trophectoderm stem (TS) and extra-embryonic endoderm (XEN) stem cell lines that were derived from the inner cell mass (ICM), TE and PrE, respectively. As an initial indicator of the chromatin state, we assessed the replication timing of a cohort of genes in each cell type, based on data that expressed genes and acetylated chromatin domains, generally, replicate early in S-phase, whereas some silent genes, hypoacetylated or condensed chromatin tend to replicate later. We found that many lineage-specific genes replicate early in ES, TS and XEN cells, which was consistent with a broadly 'accessible' chromatin that was reported previously for multiple ES cell lines. Close inspection of these profiles revealed differences between ES, TS and XEN cells that were consistent with their differing lineage affiliations and developmental potential. A comparative analysis of modified histones at the promoters of individual genes showed that in TS and ES cells many lineage-specific regulator genes are co-marked with modifications associated with active (H4ac, H3K4me2, H3K9ac) and repressive (H3K27me3) chromatin. However, in XEN cells several of these genes were marked solely by repressive modifications (such as H3K27me3, H4K20me3). Consistent with TS and XEN having a restricted developmental potential, we show that these cells selectively reprogramme somatic cells to induce the de novo expression of genes associated with extraembryonic differentiation. Conclusions These data provide evidence that the diversification of defined embryonic and extra-embryonic lineages is accompanied by chromatin remodelling at specific loci. Stem cell lines from the ICM, TE and PrE can each dominantly reprogramme somatic cells but reset gene expression differently, reflecting their separate lineage identities and increasingly restricted developmental potentials.
Issue Date: 12-Jan-2010
Date of Acceptance: 12-Jan-2010
URI: http://hdl.handle.net/10044/1/71588
DOI: https://doi.org/10.1186/1756-8935-3-1
ISSN: 1756-8935
Publisher: BioMed Central
Journal / Book Title: Epigenetics & Chromatin
Volume: 3
Issue: 1
Copyright Statement: © 2010 Santos 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: Biotechnology and Biological Sciences Research Council (BBSRC)
Funder's Grant Number: BB/G011117/1
Keywords: Science & Technology
Life Sciences & Biomedicine
Genetics & Heredity
IMPRINTED X-INACTIVATION
DEVELOPMENTAL REGULATORS
VISCERAL ENDODERM
DNA-REPLICATION
GENE-EXPRESSION
E-CADHERIN
ES CELLS
DIFFERENTIATION
TROPHECTODERM
TRANSCRIPTION
Science & Technology
Life Sciences & Biomedicine
Genetics & Heredity
IMPRINTED X-INACTIVATION
DEVELOPMENTAL REGULATORS
VISCERAL ENDODERM
DNA-REPLICATION
GENE-EXPRESSION
E-CADHERIN
ES CELLS
DIFFERENTIATION
TROPHECTODERM
TRANSCRIPTION
0604 Genetics
Publication Status: Published
Article Number: 1
Online Publication Date: 2010-01-12
Appears in Collections:Division of Surgery
Clinical Sciences
National Heart and Lung Institute
Molecular Sciences



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