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

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


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Nucleus / metabolism*
  • Chromatin / metabolism
  • Epigenetic Repression / genetics*
  • Histones / metabolism
  • Jumonji Domain-Containing Histone Demethylases / genetics
  • Jumonji Domain-Containing Histone Demethylases / metabolism*
  • Methylation
  • Mice
  • Neuregulins / metabolism*
  • Promoter Regions, Genetic / genetics*
  • Receptor, ErbB-3 / genetics
  • Receptor, ErbB-3 / metabolism*
  • Schwann Cells / metabolism*


  • Chromatin
  • Histones
  • Neuregulins
  • Jumonji Domain-Containing Histone Demethylases
  • Kdm6b protein, mouse
  • ErbB3 protein, mouse
  • Receptor, ErbB-3