A genetic compensatory mechanism regulated by <i>Jun</i> and <i>Mef2d</i> modulates the expression of distinct class IIa <i>Hdacs</i> to ensure peripheral nerve myelination and repair.

ABSTRACT: 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 to

SUBMITTER: Velasco-Aviles S 

PROVIDER: S-EPMC8853665 | biostudies-literature | 2022 Jan

REPOSITORIES: biostudies-literature