Chromatin remodeler Ep400 ensures oligodendrocyte survival and is required for myelination in the vertebrate central nervous system

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Details zur Publikation

Autorinnen und Autoren: Elsesser O, Fröb F, Küspert M, Tamm ER, Fujii T, Fukunaga R, Wegner M
Zeitschrift: Nucleic acids research
Jahr der Veröffentlichung: 2019
Band: 47
Heftnummer: 12
Seitenbereich: 6208-6224
ISSN: 1362-4962


Abstract

Differentiating oligodendrocytes generate myelin to ensure rapid saltatory conduction in the vertebrate central nervous system. Although oligodendroglial differentiation and myelination are accompanied by dramatic chromatin reorganizations, previously studied chromatin remodelers had only limited direct effects on the process. To study the functional significance of chromatin changes for myelination and identify relevant remodelers, we deleted Ep400, the central ATP-hydrolyzing subunit of the TIP60/EP400 complex, at defined times of mouse oligodendrocyte development. Whereas Ep400-deficient oligodendrocyte precursors develop normally, terminal differentiation and myelination are dramatically impaired. Mechanistically, Ep400 interacts with transcription factor Sox10, binds to regulatory regions of the Myrf gene and is required to induce this central transcriptional regulator of the myelination program. In addition to reduced and aberrant myelin formation, oligodendrocytes exhibit increased DNA damage and apoptosis so that numbers never reach wildtype levels during the short lifespan of Ep400-deficient mice. Ep400 deletion in already mature oligodendrocytes remains phenotypically inapparent arguing that Ep400 is dispensable for myelin maintenance. Given its essential function in myelin formation, modulation of Ep400 activity may be beneficial in conditions such as multiple sclerosis where this process is compromised.


FAU-Autorinnen und Autoren / FAU-Herausgeberinnen und Herausgeber

Elsesser, Olga Dr.
Lehrstuhl für Biochemie und Pathobiochemie
Thiele, Franziska Dr.
Lehrstuhl für Biochemie und Pathobiochemie
Küspert, Melanie Dr.
Lehrstuhl für Biochemie und Pathobiochemie
Wegner, Michael Prof. Dr.
Lehrstuhl für Biochemie und Pathobiochemie


Einrichtungen weiterer Autorinnen und Autoren

Osaka University of Pharmaceutical Sciences
Universität Regensburg


Zitierweisen

APA:
Elsesser, O., Fröb, F., Küspert, M., Tamm, E.R., Fujii, T., Fukunaga, R., & Wegner, M. (2019). Chromatin remodeler Ep400 ensures oligodendrocyte survival and is required for myelination in the vertebrate central nervous system. Nucleic acids research, 47(12), 6208-6224. https://dx.doi.org/10.1093/nar/gkz376

MLA:
Elsesser, Olga, et al. "Chromatin remodeler Ep400 ensures oligodendrocyte survival and is required for myelination in the vertebrate central nervous system." Nucleic acids research 47.12 (2019): 6208-6224.

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Zuletzt aktualisiert 2019-31-07 um 22:08