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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...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
eLife Sciences Publications, Ltd
2022
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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. |
format | Online Article Text |
id | pubmed-8853665 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | eLife Sciences Publications, Ltd |
record_format | MEDLINE/PubMed |
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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