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J Neurosci. 2015 Jan 7;35(1):352-65. doi: 10.1523/JNEUROSCI.2606-14.2015.

Chromatin landscape defined by repressive histone methylation during oligodendrocyte differentiation.

Author information

1
Department of Neuroscience.
2
Bioinformatics Laboratory, Department of Medicine, and.
3
Institute of Neuropathology, University Hospital Münster, D-48149 Münster, Germany.
4
Department of Neuroscience, Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York 10029, and.
5
Department of Neuroscience, Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York 10029, and patrizia.casaccia@mssm.edu.

Abstract

In many cell types, differentiation requires an interplay between extrinsic signals and transcriptional changes mediated by repressive and activating histone modifications. Oligodendrocyte progenitors (OPCs) are electrically responsive cells receiving synaptic input. The differentiation of these cells into myelinating oligodendrocytes is characterized by temporal waves of gene repression followed by activation of myelin genes and progressive decline of electrical responsiveness. In this study, we used chromatin isolated from rat OPCs and immature oligodendrocytes, to characterize the genome-wide distribution of the repressive histone marks, H3K9me3 and H3K27me3, during differentiation. Although both marks were present at the OPC stage, only H3K9me3 marks (but not H3K27me3) were found to be increased during differentiation, at genes related to neuronal lineage and regulation of membrane excitability. Consistent with these findings, the levels and activity of H3K9 methyltransferases (H3K9 HMT), but not H3K27 HMT, increased more prominently upon exposure to oligodendrocyte differentiating stimuli and were detected in stage-specific repressive protein complexes containing the transcription factors SOX10 or YY1. Silencing H3K9 HMT, but not H3K27 HMT, impaired oligodendrocyte differentiation and functionally altered the response of oligodendrocytes to electrical stimulation. Together, these results identify repressive H3K9 methylation as critical for gene repression during oligodendrocyte differentiation.

KEYWORDS:

ChIP-seq; epigenetics; myelin; potassium channel

PMID:
25568127
PMCID:
PMC4287153
DOI:
10.1523/JNEUROSCI.2606-14.2015
[Indexed for MEDLINE]
Free PMC Article

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