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

Franziska Fröb, Elisabeth Sock, Ernst. R. Tamm, Anna-Lena Saur, Simone Hillgärtner, Trevor J. Williams, Toshihiro Fujii, Rikiro Fukunaga and Michael Wegner ()
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Franziska Fröb: Friedrich-Alexander-Universität Erlangen-Nürnberg
Elisabeth Sock: Friedrich-Alexander-Universität Erlangen-Nürnberg
Ernst. R. Tamm: Universität Regensburg
Anna-Lena Saur: Friedrich-Alexander-Universität Erlangen-Nürnberg
Simone Hillgärtner: Friedrich-Alexander-Universität Erlangen-Nürnberg
Trevor J. Williams: UC Denver
Toshihiro Fujii: Osaka University of Pharmaceutical Sciences
Rikiro Fukunaga: Osaka University of Pharmaceutical Sciences
Michael Wegner: Friedrich-Alexander-Universität Erlangen-Nürnberg

Nature Communications, 2019, vol. 10, issue 1, 1-14

Abstract: 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.

Date: 2019
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DOI: 10.1038/s41467-019-10287-w

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