RRC ID 56697
Author Fröb F, Sock E, Tamm ER, Saur AL, Hillgärtner S, Williams TJ, Fujii T, Fukunaga R, Wegner M.
Title Ep400 deficiency in Schwann cells causes persistent expression of early developmental regulators and peripheral neuropathy.
Journal Nat Commun
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.
Volume 10(1)
Pages 2361
Published 2019-5-29
DOI 10.1038/s41467-019-10287-w
PII 10.1038/s41467-019-10287-w
PMID 31142747
PMC PMC6541636
MeSH 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*
IF 11.878
Times Cited 1
Mice RBRC03987