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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 Gallar
dc.contributor.authorArthur-Farraj, Peter
dc.contributor.authorGomez-Sanchez, Jose
dc.contributor.authorCabedo, Hugo
dc.date.accessioned2022-02-26T02:02:11Z
dc.date.available2022-02-26T02:02:11Z
dc.date.issued2022-01-25
dc.identifier.issn2050-084X
dc.identifier.otherPMC8853665
dc.identifier.other35076395
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/334467
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.languageeng
dc.publishereLife Sciences Publications Ltd
dc.rightsAttribution 4.0 International
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.sourcenlmid: 101579614
dc.sourceessn: 2050-084X
dc.subjectCell biology
dc.subjectNerve regeneration
dc.subjectMouse
dc.subjectRat
dc.subjectNeuroscience
dc.subjectSchwann cells
dc.subjectMyelin
dc.subjectGene Compensation
dc.subjectNerve Development
dc.subjectClass Ii Hdacs
dc.subjectSchwann Cells
dc.subjectPeripheral Nerves
dc.subjectAnimals
dc.subjectMice
dc.subjectHistone Deacetylases
dc.subjectGene Expression Regulation
dc.subjectGenes, jun
dc.subjectFemale
dc.subjectMale
dc.subjectMEF2 Transcription Factors
dc.subjectRemyelination
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.updated2022-02-26T02:02:08Z
prism.publicationNameeLife
prism.volume11
dc.identifier.doi10.17863/CAM.81884
dcterms.dateAccepted2022-01-24
rioxxterms.versionofrecord10.7554/eLife.72917
rioxxterms.versionVoR
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by/4.0/
dc.contributor.orcidArthur-Farraj, Peter [0000-0002-1239-9392]
dc.identifier.eissn2050-084X
pubs.funder-project-idWellcome Trust (UNS38871)
cam.issuedOnline2022-01-25


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Attribution 4.0 International
Except where otherwise noted, this item's licence is described as Attribution 4.0 International