biostudies-literatureVelasco-Aviles SISABIALConselleria de Cultura, Educación y Ciencia, Generalitat ValencianaMinisterio de Economía y CompetitividadMinisterio de Educación, Cultura y DeporteWellcome Truste72917https://www.ebi.ac.uk/biostudies/studies/S-EPMC8853665biostudies-literatureUnknown11The 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 toeLifeA genetic compensatory mechanism regulated by Jun and Mef2d modulates the expression of distinct class IIa Hdacs to ensure peripheral nerve myelination and repair.PMC8853665206634/Z/17/ZFPU16/00283PID2019-109762RB-I00UGP18-257ACIF/2 017/169BFU2016-75864RPROMETEO 2018/114UGP-2019-128Casillas-Bajo ACabedo HPatel NFrutos-Rincon LVelasco-Aviles SGomez-Sanchez JAVelasco EGallar JArthur-Farraj PfalseA genetic compensatory mechanism regulated by Jun and Mef2d modulates the expression of distinct class IIa Hdacs to ensure peripheral nerve myelination and repair.The 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 to2022-01-01T00:00:00Z2022 Jan2026-05-30T23:15:49.822Z2024-11-06T06:43:35.632ZS-EPMC88536653507639510.7554/eLife.72917