Class IIa histone deacetylases link cAMP signaling to the myelin transcriptional program of Schwann cells

Gomis-Coloma, Clara; Velasco-Aviles, Sergio; Gomez-Sanchez, Jose A.; Casillas-Bajo, Angeles; Backs, Johannes; Cabedo, Hugo

doi:10.1083/jcb.201611150

Cited by 25 publications

(49 citation statements)

References 66 publications

(113 reference statements)

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“…Accordingly, axonal regeneration is faster if Schwann cell HDAC1/2 is inactivated, but re‐myelination is impaired (Brügger et al, ). HDAC4 also suppresses c‐Jun and elevates myelin gene expression (Gomis‐Coloma et al, ). In contrast, HDAC3 upregulates negative regulators of myelination, including Id2 and Sox2, and the Notch and Hippo signaling pathways.…”

Section: Adaptive Cellular Reprogrammingmentioning

confidence: 99%

Repair Schwann cell update: Adaptive reprogramming, EMT, and stemness in regenerating nerves

Jessen

Arthur‐Farraj

2019

Glia

234

260

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Schwann cells respond to nerve injury by cellular reprogramming that generates cells specialized for promoting regeneration and repair. These repair cells clear redundant myelin, attract macrophages, support survival of damaged neurons, encourage axonal growth, and guide axons back to their targets. There are interesting parallels between this response and that found in other tissues. At the cellular level, many other tissues also react to injury by cellular reprogramming, generating cells specialized to promote tissue homeostasis and repair. And at the molecular level, a common feature possessed by Schwann cells and many other cells is the injury‐induced activation of genes associated with epithelial–mesenchymal transitions and stemness, differentiation states that are linked to cellular plasticity and that help injury‐induced tissue remodeling. The number of signaling systems regulating Schwann cell plasticity is rapidly increasing. Importantly, this includes mechanisms that are crucial for the generation of functional repair Schwann cells and nerve regeneration, although they have no or a minor role elsewhere in the Schwann cell lineage. This encourages the view that selective tools can be developed to control these particular cells, amplify their repair supportive functions and prevent their deterioration. In this review, we discuss the emerging similarities between the injury response seen in nerves and in other tissues and survey the transcription factors, epigenetic mechanisms, and signaling cascades that control repair Schwann cells, with emphasis on systems that selectively regulate the Schwann cell injury response.

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Section: Adaptive Cellular Reprogrammingmentioning

confidence: 99%

Repair Schwann cell update: Adaptive reprogramming, EMT, and stemness in regenerating nerves

Jessen

Arthur‐Farraj

2019

Glia

234

260

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“…Indeed, H3K4me3, an activating methylation mark, accumulates at enhancers of promyelinating factors such as Myrf and Olig2 and of myelin genes to promote OL myelination 24,25 . In the PNS, HDAC4, together with HDAC3, deacetylate and silence the promoter of cJun, an inducer of SC demyelination, to promote myelination 26 , however, the loss of HDAC3 leads to hypermyelination in adult mice and promotes remyelination after PNS lesion 27,28 , suggesting a dual function for HDAC3 in the myelination and remyelination processes. The PRC2 complex, which adds repressive H3K27me3 marks, also possesses a dual function: it is necessary to prevent hypermyelination, whereas it also maintains myelin integrity by repressing injury-related genes 29 .…”

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confidence: 99%

EEF1A1 deacetylation enables transcriptional activation of remyelination

et al. 2020

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Remyelination of the peripheral and central nervous systems (PNS and CNS, respectively) is a prerequisite for functional recovery after lesion. However, this process is not always optimal and becomes inefficient in the course of multiple sclerosis. Here we show that, when acetylated, eukaryotic elongation factor 1A1 (eEF1A1) negatively regulates PNS and CNS remyelination. Acetylated eEF1A1 (Ac-eEF1A1) translocates into the nucleus of myelinating cells where it binds to Sox10, a key transcription factor for PNS and CNS myelination and remyelination, to drag Sox10 out of the nucleus. We show that the lysine acetyltransferase Tip60 acetylates eEF1A1, whereas the histone deacetylase HDAC2 deacetylates eEF1A1. Promoting eEF1A1 deacetylation maintains the activation of Sox10 target genes and increases PNS and CNS remyelination efficiency. Taken together, these data identify a major mechanism of Sox10 regulation, which appears promising for future translational studies on PNS and CNS remyelination.

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“…With conditional knockout mice, Gomis‐Coloma C showed that class II HDAC4 together with HDAC5 redundantly contribute to activate the myelin transcriptional program and the formation of myelin sheath in Schwann cells in vivo (Gomis‐Coloma et al., ). Furthermore, a member of class III HDACs, SIRT2, is also expressed in SCs during developmental myelination and remyelination after nerve injury.…”

Section: Hdacs In Peripheral Nervous System Myelinationmentioning

confidence: 99%

Epigenetic regulation of myelination in health and disease

Zhang

Wang

et al. 2019

Eur J of Neuroscience

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Myelin is lipid‐rich structure that is necessary to avoid leakage of electric signals and to ensure saltatory impulse conduction along axons. Oligodendrocytes in central nervous system (CNS) and Schwann cells in peripheral nervous system (PNS) are responsible for myelin formation. Axonal demyelination after injury or diseases greatly impairs normal nervous system function. Therefore, understanding how the myelination process is programmed, coordinated, and maintained is crucial for developing therapeutic strategies for remyelination in the nervous system. Epigenetic mechanisms have been recognized as a fundamental contributor in this process. In recent years, histone modification, DNA modification, ATP‐dependent chromatin remodeling, and non‐coding RNA modulation are very active area of investigation. We will present a conceptual framework that integrates crucial epigenetic mechanisms with the regulation of oligodendrocyte and Schwann cell lineage progression during development and myelin degeneration in pathological conditions. It is anticipated that a refined understanding of the molecular basis of myelination will aid in the development of treatment strategies for debilitating disorders that involve demyelination, such as multiple sclerosis in the CNS and neuropathies in the PNS.

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Class IIa histone deacetylases link cAMP signaling to the myelin transcriptional program of Schwann cells

Cited by 25 publications

References 66 publications

Repair Schwann cell update: Adaptive reprogramming, EMT, and stemness in regenerating nerves

Repair Schwann cell update: Adaptive reprogramming, EMT, and stemness in regenerating nerves

EEF1A1 deacetylation enables transcriptional activation of remyelination

Epigenetic regulation of myelination in health and disease

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