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

Fröb F, Sock E, Tamm ER, Saur AL, Hillgärtner S, Williams TJ, Fujii T, Fukunaga R, Wegner M (2019)

Publication Type: Journal article

Publication year: 2019

Journal

Nature Communications Nature Publishing Group: Nature Communications

Book Volume: 10

DOI: 10.1038/s41467-019-10287-w

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.

Authors with CRIS profile

Franziska Thiele Lehrstuhl für Biochemie und Pathobiochemie Elisabeth Sock Lehrstuhl für Biochemie und Pathobiochemie Anna-Lena Saur Lehrstuhl für Biochemie und Pathobiochemie Simone Hillgärtner Lehrstuhl für Biochemie und Pathobiochemie Michael Wegner Lehrstuhl für Biochemie und Pathobiochemie

Involved external institutions

Universität Regensburg DE Germany (DE) University of Colorado System US United States (USA) (US) Osaka University of Pharmaceutical Sciences JP Japan (JP)

How to cite

APA:

Fröb, F., Sock, E., Tamm, E.R., Saur, A.-L., Hillgärtner, S., Williams, T.J.,... Wegner, M. (2019). Ep400 deficiency in Schwann cells causes persistent expression of early developmental regulators and peripheral neuropathy. Nature Communications, 10. https://dx.doi.org/10.1038/s41467-019-10287-w

MLA:

Fröb, Franziska, et al. "Ep400 deficiency in Schwann cells causes persistent expression of early developmental regulators and peripheral neuropathy." Nature Communications 10 (2019).

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