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Cited by 40Genomics and Chromatin DynamicsEpigenetics and DNA MethylationDevelopmental Biology and Gene Regulation

The function of chromatin modifiers in lineage commitment and cell fate specification

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Signolet, Jason, Hendrich, Brian·2015·The FEBS Journal
DOI 10.1111/febs.13132PMC PMC4508967
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Abstract

Proteins that modify the structure of chromatin are known to be important for various aspects of metazoan biology including development, disease and possibly ageing. Yet functional details of why these proteins are important, i.e. how their action influences a given biological process, are lacking. While it is now possible to describe the biochemistry of how these proteins remodel chromatin, their chromatin binding profiles in cell lines, or gene expression changes upon loss of a given protein, in very few cases has this easily translated into an understanding of how the function of that protein actually influences a developmental process. Given that many chromatin modifying proteins will largely exert their influence through control of gene expression, it is useful to consider developmental processes as changes in the gene regulatory network (GRN), with each cell type exhibiting a unique gene expression profile. In this essay we consider the impact of two abundant and highly conserved chromatin modifying complexes, namely the nucleosome remodelling and deacetylation (Nu RD) complex and the polycomb repressive complex 2 (PRC 2), on the change in GRN s associated with lineage commitment during early mammalian development. We propose that while the Nu RD complex limits the stability of cell states and defines the developmental trajectory between two stable states, PRC 2 activity is important for stabilizing a new GRN once established. Although these two complexes display different biochemical activities, chromatin binding profiles and mutant phenotypes, we propose a model to explain how they cooperate to facilitate the transition through cell states that is development.

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Cited by

Sorted by citations

Authors
Signolet, J., & Hendrich, B.
Affiliations
Wellcome/MRC Cambridge Stem Cell Institute (GB)
Corresponding author
Hendrich, Brian
ORCID
Hendrich, Brian
Venue
The FEBS Journal
Publisher
Wiley
Published
2014-11-20
Volume
282
Issue
9
Pages
1692-1702
ISSN
  • 1742-464X (ISSN-L)
  • 1742-4658
DOI
10.1111/febs.13132
PMC
PMC4508967
OpenAlex
W2113830687
Cited by
40
References
5
Citations by year
2026: 3 · 2025: 3 · 2024: 1 · 2023: 3 · 2022: 1 · 2021: 4 · 2020: 3 · 2019: 2 · 2018: 4 · 2017: 4 · 2016: 6 · 2015: 5 · 2014: 1
FWCI
0.50
Type
journal article
Language
en
Open access
Licence
Locations
  • FEBS Journal (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Apollo (University of Cambridge) (submittedVersion, cc-by)
Funders
  • Wellcome Trust (WT098021MA)
  • Medical Research Council
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
Keywords
chromatin modifiers, lineage commitment, cell fate specification, NuRD complex, polycomb repressive complex 2, gene regulatory networks, chromatin remodeling, histone deacetylation, developmental trajectories, early mammalian development
MeSH terms
Animals, Chromatin, Cell Lineage, Mice, Gene Regulatory Networks, Embryonic Stem Cells

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