RRC ID |
56697
|
著者 |
Fröb F, Sock E, Tamm ER, Saur AL, Hillgärtner S, Williams TJ, Fujii T, Fukunaga R, Wegner M.
|
タイトル |
Ep400 deficiency in Schwann cells causes persistent expression of early developmental regulators and peripheral neuropathy.
|
ジャーナル |
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.
|
巻・号 |
10(1)
|
ページ |
2361
|
公開日 |
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
|
引用数 |
1
|
リソース情報 |
実験動物マウス |
RBRC03987 |