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

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

Author information

1
Institut für Biochemie, Emil-Fischer-Zentrum, Friedrich-Alexander-Universität Erlangen-Nürnberg, Fahrstrasse 17, 91054, Erlangen, Germany.
2
Institut für Humananatomie und Embryologie, Universität Regensburg, Universitätsstrasse 31, 93053, Regensburg, Germany.
3
Departments of Craniofacial Biology and Cell and Developmental Biology, UC Denver, Anschutz Medical Campus, 12801 East 17th Avenue, Aurora, CO, 80045, USA.
4
Department of Biochemistry, Osaka University of Pharmaceutical Sciences, 4-20-1 Nasahara, Takatsuki, Osaka, 569-1094, Japan.
5
Institut für Biochemie, Emil-Fischer-Zentrum, Friedrich-Alexander-Universität Erlangen-Nürnberg, Fahrstrasse 17, 91054, Erlangen, Germany. michael.wegner@fau.de.

Abstract

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.

PMID:
31142747
PMCID:
PMC6541636
DOI:
10.1038/s41467-019-10287-w
[Indexed for MEDLINE]
Free PMC Article

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