Repository logo
 

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


Type

Article

Change log

Authors

Signolet, Jason 

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 (NuRD) complex and the polycomb repressive complex 2 (PRC2), on the change in GRNs associated with lineage commitment during early mammalian development. We propose that while the NuRD complex limits the stability of cell states and defines the developmental trajectory between two stable states, PRC2 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.

Description

Keywords

NuRD, development, gene expression, gene regulatory network, polycomb, stem cells, Animals, Cell Lineage, Chromatin, Embryonic Stem Cells, Gene Regulatory Networks, Mice

Journal Title

FEBS J

Conference Name

Journal ISSN

1742-464X
1742-4658

Volume Title

282

Publisher

Wiley
Sponsorship
Wellcome Trust (098021/Z/11/Z)
Work in the BH Lab is supported by a Wellcome Trust Senior Research Fellowship in the Basic Biomedical Sciences held by BH, and by the Wellcome Trust – Medical Research Council Stem Cell Institute. JS was funded as a PhD student by the UK Medical Research Council during part of this work.