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Glia. 2016 Jun;64(6):977-92. doi: 10.1002/glia.22977. Epub 2016 Mar 28.

Nuc-ErbB3 regulates H3K27me3 levels and HMT activity to establish epigenetic repression during peripheral myelination.

Author information

1
Molecular Neuroscience and Neurooncology Laboratory, Geisinger Clinic, Danville, Pennsylvania.
2
Department of Systems and Computational Biology, Albert Einstein College of Medicine, Bronx, New York.

Abstract

Nuc-ErbB3 an alternative transcript from the ErbB3 locus binds to a specific DNA motif and associates with Schwann cell chromatin. Here we generated a nuc-ErbB3 knockin mouse that lacks nuc-ErbB3 expression in the nucleus without affecting the neuregulin-ErbB3 receptor signaling. Nuc-ErbB3 knockin mice exhibit hypermyelination and aberrant myelination at the paranodal region. This phenotype is attributed to de-repression of myelination associated gene transcription following loss of nuc-ErbB3 and histone H3K27me3 promoter occupancy. Nuc-ErbB3 knockin mice exhibit reduced association of H3K27me3 with myelination-associated gene promoters and increased RNA Pol-II rate of transcription of these genes. In addition, nuc-ErbB3 directly regulates levels of H3K27me3 in Schwann cells. Nuc-ErbB3 knockin mice exhibit significant decrease of histone H3K27me3 methyltransferase (HMT) activity and reduced levels of H3K27me3. Collectively, nuc-ErbB3 is a master transcriptional repressor, which regulates HMT activity to establish a repressive chromatin landscape on promoters of genes during peripheral myelination.

KEYWORDS:

PNS myelination; chromatin; transcriptional repression

PMID:
27017927
PMCID:
PMC5021170
DOI:
10.1002/glia.22977
[Indexed for MEDLINE]
Free PMC Article

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