Interpretation of Developmental Signaling at Chromatin: The Polycomb Perspective

Abstract

The Polycomb group (PcG) system represses the transcription of important developmental regulators and perpetuates this repression across multiple cell divisions. Inputs from outside the cell can influence PcG function by recruiting additional chromatin factors to PcG-regulated loci or by downregulating the PcG genes themselves. These types of PcG system modulation allow context-dependent induction of genes during development, in cancer, and in response to changes in the environment. In this review, we outline instances where molecular players in this process have been recently identified, comparing and contrasting different ways in which derepression is achieved, and projecting directions for future research.

Transcriptional repression by the Msx1 homeoprotein is associated with global redistribution of the H3K27me3 repressive mark to the nuclear periphery

“…Indeed, Msx1 genomic binding is specifically coincident with enrichment of the H3K27me3 repressive mark on repressed target genes. 15,16,18,21,25,28,49 This observation suggests that Msx1 represses gene expression through recruitment of the Polycomb repressive mark H3K27me3 to target genes at the nuclear periphery.…”

“…52 Therefore, whether a target gene is "activated" or "repressed" may depend on its sub-nuclear localization, the distribution of activator and repressor chromatin marks and components of the core transcriptional complex. 16,20,34,52 In general, our studies provide insight into the general features of how chromatin modifications contribute to the dynamic spatial and temporal control of lineage-specific target genes in diverse cell types during development.…”

“…Among these, the Polycomb proteins, which form multi-protein complexes that comprise the PRC1 and PRC2 complexes, function to repress gene expression. [15][16][17] In mammalian cells, the PRC2 complex, which includes the enzymatic component, Ezh2, as well as Suz12 and EED, imparts the repressive trimethyl mark at lysine 27 of histone H3 (H3K27me3). [18][19][20] The PRC2 complex regulates many biological processes, including differentiation, maintaining cell identity, and stem-cell plasticity.…”

A Role for Monomethylation of Histone H3-K27 in Gene Activity inDrosophila

“…The enzyme responsible for K27 tri-methylation, PRC2, is present in single-celled eukaryotes and fungal species and it is highly conserved in plants and animals (SAWARKAR and PARO 2010), where it is centrally integrated into stem cell transcriptional programs (PEREIRA et al 2010;SURFACE et al 2010;XIE et al 2014). Although H3-K27me3 is fundamentally associated with developmental gene silencing, its mechanistic consequences are incompletely understood.…”

Coordinated Regulation of Dendrite Arborization by Epigenetic Factors CDYL and EZH2

“…In particular, covalently modified histone residues, either alone or in combination, create docking sites for specific "reader" proteins, which subsequently recruit transcriptional regulators to tune up or tune down the expression level of local genes. Although several histone modifiers have been implicated in various aspects of neurobiology, such as cell death, learning, and memory (Wu et al, 2007;Nott et al, 2008;Qiu and Ghosh, 2008;Guan et al, 2009;Riccio, 2010;Sawarkar and Paro, 2010;Tea et al, 2010;Jakovcevski and Akbarian, 2012), little is known about how epigenetic mechanisms contribute to dendrite morphogenesis, a process critical for the establishment of neural circuits .…”