Authors: Sergio Velasco-Aviles, Nikiben Patel, Angeles Casillas-Bajo, Laura Frutos-Rincón, Enrique Velasco, Juana Gallar, Peter Arthur-Farraj, Jose A Gomez-Sanchez, Hugo Cabedo


  • Instituto de Neurociencias de Alicante UMH-CSIC, Spain
  • Instituto de Investigación Sanitaria y Biomédica de Alicante (ISABIAL), Spain
  • The European University of Brain and Technology-NeurotechEU, Spain
  • RICORS en enfermedades inflamatorias, Spain
  • John Van Geest Centre for Brain Repair, Department of Clinical Neurosciences, University of Cambridge, United Kingdom

Publication: eLife Sciences

Date: January 2022

Full paper: A 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 Hdac45, 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 Hdac45, 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.