Ep400 deficiency in Schwann cells causes persistent expression of early developmental regulators and peripheral neuropathy

Nat Commun. 2019 May 29;10(1):2361. doi: 10.1038/s41467-019-10287-w.


Schwann cells ensure efficient nerve impulse conduction in the peripheral nervous system. Their development is accompanied by defined chromatin changes, including variant histone deposition and redistribution. To study the importance of variant histones for Schwann cell development, we altered their genomic distribution by conditionally deleting Ep400, the central subunit of the Tip60/Ep400 complex. Ep400 absence causes peripheral neuropathy in mice, characterized by terminal differentiation defects in myelinating and non-myelinating Schwann cells and immune cell activation. Variant histone H2A.Z is differently distributed throughout the genome and remains at promoters of Tfap2a, Pax3 and other transcriptional regulator genes with transient function at earlier developmental stages. Tfap2a deletion in Ep400-deficient Schwann cells causes a partial rescue arguing that continued expression of early regulators mediates the phenotypic defects. Our results show that proper genomic distribution of variant histones is essential for Schwann cell differentiation, and assign importance to Ep400-containing chromatin remodelers in the process.

Publication types

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

MeSH terms

  • Animals
  • Chromatin Assembly and Disassembly
  • DNA Helicases
  • DNA-Binding Proteins
  • Gene Expression Regulation, Developmental
  • Histones / metabolism*
  • Mice
  • Mice, Transgenic
  • PAX3 Transcription Factor / genetics
  • PAX3 Transcription Factor / metabolism
  • Peripheral Nervous System Diseases / genetics*
  • Peripheral Nervous System Diseases / metabolism
  • Peripheral Nervous System Diseases / pathology
  • Promoter Regions, Genetic
  • Schwann Cells / metabolism*
  • Sciatic Nerve / metabolism*
  • Sciatic Nerve / pathology
  • Transcription Factor AP-2 / genetics
  • Transcription Factor AP-2 / metabolism
  • Transcription Factors / genetics*


  • DNA-Binding Proteins
  • Histones
  • PAX3 Transcription Factor
  • Tfap2a protein, mouse
  • Transcription Factor AP-2
  • Transcription Factors
  • Pax3 protein, mouse
  • DNA Helicases
  • Ep400 protein, mouse