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Epigenomes 2017, 1(3), 21; https://doi.org/10.3390/epigenomes1030021

Switch-Like Roles for Polycomb Proteins from Neurodevelopment to Neurodegeneration

Department of Translational Psychiatry, Max Planck Institute of Psychiatry, 80804 Munich, Germany
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Author to whom correspondence should be addressed.
Academic Editor: Luciano Di Croce
Received: 16 October 2017 / Revised: 13 November 2017 / Accepted: 27 November 2017 / Published: 1 December 2017
(This article belongs to the Special Issue Polycomb and Trithorax Group of Proteins in Development and Disease)
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Abstract

Polycomb Group (PcG) proteins are best-known for maintaining repressive or active chromatin states that are passed on across multiple cell divisions, and thus sustain long-term memory of gene expression. PcG proteins engage different, partly gene- and/or stage-specific, mechanisms to mediate spatiotemporal gene expression during central nervous system development. In the course of this, PcG proteins bind to various cis-regulatory sequences (e.g., promoters, enhancers or silencers) and coordinate, as well the interactions between distantly separated genomic regions to control chromatin function at different scales ranging from compaction of the linear chromatin to the formation of topological hubs. Recent findings show that PcG proteins are involved in switch-like changes in gene expression states of selected neural genes during the transition from multipotent to differentiating cells, and then to mature neurons. Beyond neurodevelopment, PcG proteins sustain mature neuronal function and viability, and prevent progressive neurodegeneration in mice. In support of this view, neuropathological findings from human neurodegenerative diseases point to altered PcG functions. Overall, improved insight into the multiplicity of PcG functions may advance our understanding of human neurodegenerative diseases and ultimately pave the way to new therapies. View Full-Text
Keywords: polycomb proteins; neurodevelopment; embryonic stem cells; neural stem and progenitor cells; chromatin bivalency; neural cell fate; neuronal maturation; neurodegeneration polycomb proteins; neurodevelopment; embryonic stem cells; neural stem and progenitor cells; chromatin bivalency; neural cell fate; neuronal maturation; neurodegeneration
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Hoffmann, A.; Sportelli, V.; Ziller, M.; Spengler, D. Switch-Like Roles for Polycomb Proteins from Neurodevelopment to Neurodegeneration. Epigenomes 2017, 1, 21.

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