EEF1A1 deacetylation enables transcriptional activation of remyelination.

Duman, Mert; Vaquié, Adrien; Nocera, Gianluigi; Heller, Manfred; Stumpe, Michael; Siva Sankar, Devanarayanan; Dengjel, Jörn; Meijer, Dies; Yamaguchi, Teppei; Matthias, Patrick; Zeis, Thomas; Schaeren-Wiemers, Nicole; Hayoz, Antoinette; Ruff, Sophie; Jacob, Claire (2020). EEF1A1 deacetylation enables transcriptional activation of remyelination. Nature Communications, 11(1), p. 3420. Springer Nature 10.1038/s41467-020-17243-z

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Remyelination of the peripheral and central nervous systems (PNS and CNS, respectively) is a prerequisite for functional recovery after lesion. However, this process is not always optimal and becomes inefficient in the course of multiple sclerosis. Here we show that, when acetylated, eukaryotic elongation factor 1A1 (eEF1A1) negatively regulates PNS and CNS remyelination. Acetylated eEF1A1 (Ac-eEF1A1) translocates into the nucleus of myelinating cells where it binds to Sox10, a key transcription factor for PNS and CNS myelination and remyelination, to drag Sox10 out of the nucleus. We show that the lysine acetyltransferase Tip60 acetylates eEF1A1, whereas the histone deacetylase HDAC2 deacetylates eEF1A1. Promoting eEF1A1 deacetylation maintains the activation of Sox10 target genes and increases PNS and CNS remyelination efficiency. Taken together, these data identify a major mechanism of Sox10 regulation, which appears promising for future translational studies on PNS and CNS remyelination.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR)
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DCR Services > Core Facility Massenspektrometrie- und Proteomics-Labor
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > Unit Childrens Hospital > Protein- und Zellbiologie

UniBE Contributor:

Heller, Manfred

Subjects:

600 Technology > 610 Medicine & health

ISSN:

2041-1723

Publisher:

Springer Nature

Language:

English

Submitter:

Marla Rittiner

Date Deposited:

29 Dec 2020 10:10

Last Modified:

13 Mar 2021 11:54

Publisher DOI:

10.1038/s41467-020-17243-z

PubMed ID:

32647127

BORIS DOI:

10.48350/150162

URI:

https://boris.unibe.ch/id/eprint/150162

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