Class IIa HDACs in myelination

Velasco-Aviles, Sergio; Gomez-Sanchez, Jose A.; Cabedo, Hugo

doi:10.18632/aging.101443

Cited by 2 publications

(2 citation statements)

References 7 publications

(9 reference statements)

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“…Nuclear HDAC4 recruits the complex NcoR1/HDAC3 and deacetylates histone three on the promoter of Jun , repressing its expression. At the same time HDAC4 promotes Krox-20 expression and activation of the myelination program ( Velasco-Aviles et al, 2018 ). In vivo, Hdac5 is able to partially compensate for the loss of Hdac4 expression in Schwann cells and only the removal of both Hdac4 and Hdac5 from Schwann cells leads to an obvious myelination delay.…”

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confidence: 99%

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

Patel

Casillas-Bajo

et al. 2022

eLife

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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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Section: Introductionmentioning

confidence: 99%

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

Patel

Casillas-Bajo

et al. 2022

eLife

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“…Nuclear HDAC4 recruits the complex NcoR1/HDAC3 and deacetylates histone 3 on the promoter of c-Jun , repressing its expression. At the same time HDAC4 promotes Krox20 expression and activation of the myelination program (Velasco-Aviles et al, 2018). In vivo , HDAC5 is able to compensate for the loss of HDAC4 expression in Schwann cells and only the removal of both HDAC4 and HDAC5 from Schwann cells leads to myelination defects.…”

Section: Introductionmentioning

confidence: 99%

A genetic compensatory mechanism regulated by c-Jun and Mef2d modulates the expression of distinct class IIa HDACs to ensure peripheral nerve myelination and repair

Cabedo

Velasco-Aviles

Patel

et al. 2021

Preprint

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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 HDCA9. 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, a c-Jun dependent mechanism induces the compensatory overexpression of HDAC7 permitting, although with a delay, the formation of a 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 mis- expressed 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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Class IIa HDACs in myelination

Cited by 2 publications

References 7 publications

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

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

A genetic compensatory mechanism regulated by c-Jun and Mef2d modulates the expression of distinct class IIa HDACs to ensure peripheral nerve myelination and repair

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