Abstract

In embryonic stem cells (ESCs), silent genes with major developmental functions display a unique epigenetic state in which strong and broad binding by Polycomb repressive complexes (PRCs) is accompanied by the presence of poised RNA polymerase II (RNAPII) and activating histone marks (e.g. H3K4me3) (Azuara et al , 2006; Bernstein et al , 2006; Stock et al , 2007; Brookes et al , 2012). It has been suggested that the plasticity and broad differentiation potential of pluripotent cells might rely, at least partly, on this unique epigenetic state (Bernstein et al , 2006; Stock et al , 2007). In their recent study, Pombo and colleagues (Ferrai et al , 2017) show that a similar epigenetic state can be found at a subset of major developmental genes throughout the differentiation of ESCs into neurons, providing novel and exciting insights into the molecular basis of cellular plasticity in differentiated cells.

Highlights

  • It has been suggested that the presence of bivalent chromatin and poised RNA polymerase II (RNAPII) at these developmental genes might prime their subsequent activation during embryonic stem cells (ESCs) differentiation (Bernstein et al, 2006; Stock et al, 2007)

  • It has been hypothesized that the broad differentiation potential of pluripotent cells might depend, at least partly, on the unique epigenetic features that major developmental genes display in these cells

  • It is still possible that the pervasiveness of poised RNAPII/Polycomb repressive complexes (PRCs) genes in ESCs contributes to their pluripotency

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Summary

Introduction

In embryonic stem cells (ESCs), silent genes with major developmental functions display a unique epigenetic state in which strong and broad binding by Polycomb repressive complexes (PRCs) is accompanied by the presence of poised RNA polymerase II (RNAPII) and activating histone marks (e.g. H3K4me3) (Azuara et al, 2006; Bernstein et al, 2006; Stock et al, 2007; Brookes et al, 2012). Genes with major regulatory functions during the acquisition of specific somatic cellular identities are silent or expressed at low levels in ESCs. these genes are frequently embedded within broad PRC-bound domains. The promoter regions of these major cell-identity genes were previously shown to be occupied by H3K4me3, an activating histone mark, and were termed as “bivalent” promoters (Azuara et al, 2006; Bernstein et al, 2006).

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