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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 Hdac4, 5, and 7 but not Hdac9. Here, we show that a transcription factor regulated genetic compensatory mechanism within this family of proteins, blocks negati...

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Autores principales: Velasco-Aviles, Sergio, Patel, Nikiben, Casillas-Bajo, Angeles, Frutos-Rincón, Laura, Velasco, Enrique, Gallar, Juana, Arthur-Farraj, Peter, Gomez-Sanchez, Jose A, Cabedo, Hugo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8853665/
https://www.ncbi.nlm.nih.gov/pubmed/35076395
http://dx.doi.org/10.7554/eLife.72917
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author Velasco-Aviles, Sergio
Patel, Nikiben
Casillas-Bajo, Angeles
Frutos-Rincón, Laura
Velasco, Enrique
Gallar, Juana
Arthur-Farraj, Peter
Gomez-Sanchez, Jose A
Cabedo, Hugo
author_facet Velasco-Aviles, Sergio
Patel, Nikiben
Casillas-Bajo, Angeles
Frutos-Rincón, Laura
Velasco, Enrique
Gallar, Juana
Arthur-Farraj, Peter
Gomez-Sanchez, Jose A
Cabedo, Hugo
author_sort Velasco-Aviles, Sergio
collection PubMed
description 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 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.
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spelling pubmed-88536652022-02-22 A genetic compensatory mechanism regulated by Jun and Mef2d modulates the expression of distinct class IIa Hdacs to ensure peripheral nerve myelination and repair Velasco-Aviles, Sergio Patel, Nikiben Casillas-Bajo, Angeles Frutos-Rincón, Laura Velasco, Enrique Gallar, Juana Arthur-Farraj, Peter Gomez-Sanchez, Jose A Cabedo, Hugo eLife Cell Biology 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 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. eLife Sciences Publications, Ltd 2022-01-25 /pmc/articles/PMC8853665/ /pubmed/35076395 http://dx.doi.org/10.7554/eLife.72917 Text en © 2022, Velasco-Aviles, Patel et al https://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Cell Biology
Velasco-Aviles, Sergio
Patel, Nikiben
Casillas-Bajo, Angeles
Frutos-Rincón, Laura
Velasco, Enrique
Gallar, Juana
Arthur-Farraj, Peter
Gomez-Sanchez, Jose A
Cabedo, Hugo
A genetic compensatory mechanism regulated by Jun and Mef2d modulates the expression of distinct class IIa Hdacs to ensure peripheral nerve myelination and repair
title A genetic compensatory mechanism regulated by Jun and Mef2d modulates the expression of distinct class IIa Hdacs to ensure peripheral nerve myelination and repair
title_full A genetic compensatory mechanism regulated by Jun and Mef2d modulates the expression of distinct class IIa Hdacs to ensure peripheral nerve myelination and repair
title_fullStr A genetic compensatory mechanism regulated by Jun and Mef2d modulates the expression of distinct class IIa Hdacs to ensure peripheral nerve myelination and repair
title_full_unstemmed A genetic compensatory mechanism regulated by Jun and Mef2d modulates the expression of distinct class IIa Hdacs to ensure peripheral nerve myelination and repair
title_short A genetic compensatory mechanism regulated by Jun and Mef2d modulates the expression of distinct class IIa Hdacs to ensure peripheral nerve myelination and repair
title_sort genetic compensatory mechanism regulated by jun and mef2d modulates the expression of distinct class iia hdacs to ensure peripheral nerve myelination and repair
topic Cell Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8853665/
https://www.ncbi.nlm.nih.gov/pubmed/35076395
http://dx.doi.org/10.7554/eLife.72917
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