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dc.contributor.authorVelasco-Aviles, Sergio
dc.contributor.authorPatel, Nikiben
dc.contributor.authorCasillas-Bajo, Angeles
dc.contributor.authorFrutos-Rincón, Laura
dc.contributor.authorVelasco-Serna, Enrique
dc.contributor.authorGallar, Juana
dc.contributor.authorArthur-Farraj, Peter
dc.contributor.authorGomez-Sanchez, Jose A
dc.contributor.authorCabedo, Hugo
dc.date.accessioned2022-02-18T03:30:46Z
dc.date.available2022-02-18T03:30:46Z
dc.date.issued2022-01-25
dc.date.submitted2021-08-09
dc.identifier.issn2050-084X
dc.identifier.other72917
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/334189
dc.description.abstractThe class IIa histone deacetylases (HDACs) have pivotal roles in the development of different tissues. Of this family, Schwann cells express Hdac4, 5 and 7 but not Hdac9. Here we show that a transcription factor regulated genetic compensatory mechanism within this family of proteins, blocks negative regulators of myelination ensuring peripheral nerve developmental myelination and remyelination after injury. Thus, when Hdac4 and 5 are knocked-out from Schwann cells in mice, a JUN-dependent mechanism induces the compensatory overexpression of Hdac7 permitting, although with a delay, the formation of the myelin sheath. When Hdac4,5 and 7 are simultaneously removed, the Myocyte-specific enhancer-factor d (MEF2D) binds to the promoter and induces the de novo expression of Hdac9, and although several melanocytic lineage genes are misexpressed and Remak bundle structure is disrupted, myelination proceeds after a long delay. Thus, our data unveil a finely tuned compensatory mechanism within the class IIa Hdac family, coordinated by distinct transcription factors, that guarantees the ability of Schwann cells to myelinate during development and remyelinate after nerve injury.
dc.languageen
dc.publishereLife Sciences Publications, Ltd
dc.subjectResearch Article
dc.subjectCell Biology
dc.subjectNeuroscience
dc.subjectmyelin
dc.subjectSchwann cells
dc.subjectclass II HDACs
dc.subjectgene compensation
dc.subjectnerve development
dc.subjectnerve regeneration
dc.subjectMouse
dc.subjectRat
dc.titleA genetic compensatory mechanism regulated by Jun and Mef2d modulates the expression of distinct class IIa Hdacs to ensure peripheral nerve myelination and repair.
dc.typeArticle
dc.date.updated2022-02-18T03:30:40Z
prism.publicationNameElife
prism.volume11
dc.identifier.doi10.17863/CAM.81600
dcterms.dateAccepted2022-01-24
rioxxterms.versionofrecord10.7554/eLife.72917
rioxxterms.versionVoR
rioxxterms.licenseref.urihttp://creativecommons.org/licenses/by/4.0/
datacite.contributor.supervisoreditor: Nave, Klaus-Armin
datacite.contributor.supervisorsenior_editor: Dulac, Catherine
dc.contributor.orcidPatel, Nikiben [0000-0002-0129-7622]
dc.contributor.orcidArthur-Farraj, Peter [0000-0002-1239-9392]
dc.contributor.orcidGomez-Sanchez, Jose A [0000-0002-6746-1800]
dc.contributor.orcidCabedo, Hugo [0000-0002-1322-6290]
dc.identifier.eissn2050-084X
pubs.funder-project-idWellcome Trust (UNS38871)
cam.issuedOnline2022-01-25


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