Epigenetic regulation of myelination in health and disease

Abstract

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.

Conditional Loss of BAF (mSWI/SNF) Scaffolding Subunits Affects Specification and Proliferation of Oligodendrocyte Precursors in Developing Mouse Forebrain

“…Therefore, ablation of such chromatin and epigenetic factors is expected to call forth structural and functional impairment in the developing or adult brain. Indeed, the impaired development of OL lineage caused by defective chromatin and epigenetic regulation of the various steps involved, is linked to pathophysiological changes leading to neurodevelopmental and neurodegenerative disorders (Maki et al, 2013;Ohtomo et al, 2018;Lu et al, 2019;Berry et al, 2020;Samudyata et al, 2020). Thus, it is plausible that the reported role of BAF155 and BAF170 in OL development (this study) partly highlights the white matter anomalies associated with documented syndromic and non-syndromic disorders associated with BAF complex dysfunction (Sokpor et al, 2017).…”

Chronic Exposure to Alcohol Inhibits New Myelin Generation in Adult Mouse Brain

“…Upon the initiation of differentiation, OPCs need to change morphologically and transcriptionally. Thus, the epigenetic regulators are recognized as an important indicator for OPC differentiation (Huang et al, 2015;Lu et al, 2019). Histone deacetylases (HDACs) are responsible for histone acetylation, and the expression of HDACs is linked to transcriptional repression of a number of myelination inhibitory genes (Shen et al, 2008).…”

Epigenetic regulation of oligodendrocyte differentiation: From development to demyelinating disorders

“…In OL lineage, histone acetyltransferase CREBBP (also known as CBP) has been reported to be required for the specification of OPCs from NSCs, through H3K9/14ac (Wang et al, ), yet the genome‐wide profiling of acetylation at individual lysine residues in OPC differentiation has not been thoroughly examined. Nevertheless, many studies have investigated the overall role of histone acetylation and deacetylation using pharmacological inhibition of different classes of HDACs or OL‐specific genetic ablation of these molecules (Lu et al, ; Tiane et al, ). For instance, HDAC2 has also been shown to constitute a repressive checkpoint for Sox10 expression in neonatal NSCs and OPCs (Castelo‐Branco et al, ).…”