Chromatin remodeling in oligodendrogenesis.

E V Antontseva,N P Bondar

doi:10.18699/vj21.064

Abstract

Oligodendrocytes are one type of glial cells responsible for myelination and providing trophic support for axons in the central nervous system of vertebrates. Thanks to myelin, the speed of electrical-signal conduction increases several hundred-fold because myelin serves as a kind of electrical insulator of nerve f ibers and allows for quick saltatory conduction of action potentials through Ranvier nodes, which are devoid of myelin. Given that different parts of the central nervous system are myelinated at different stages of development and most regions contain both myelinated and unmyelinated axons, it is obvious that very precise mechanisms must exist to control the myelination of individual axons. As they go through the stages of specif ication and differentiation – from multipotent neuronal cells in the ventricular zone of the neural tube to mature myelinating oligodendrocytes as well as during migration along blood vessels to their destination – cells undergo dramatic changes in the pattern of gene expression. These changes require precisely spatially and temporally coordinated interactions of various transcription factors and epigenetic events that determine the regulatory landscape of chromatin. Chromatin remodeling substantially affects transcriptional activity of genes. The main component of chromatin is the nucleosome, which, in addition to the structural function, performs a regulatory one and serves as a general repressor of genes. Changes in the type, position, and local density of nucleosomes require the action of specialized ATPdependent chromatin-remodeling complexes, which use the energy of ATP hydrolysis for their activity. Mutations in the genes encoding proteins of the remodeling complexes are often accompanied by serious disorders at early stages of embryogenesis and are frequently identif ied in various cancers. According to the domain arrangement of the ATP-hydrolyzing subunit, most of the identif ied ATP-dependent chromatin-remodeling complexes are classif ied into four subfamilies: SWI/SNF, CHD, INO80/SWR, and ISWI. In this review, we discuss the roles of these subunits of the different subfamilies at different stages of oligodendrogenesis

Highlights

Until recently, in the research on the workings of the brain, the central role in the functioning of the central nervous system has been assigned to neurons, and various pathological conditions have been regarded as a result of impaired functioning of neurons
A genome-wide search for Chd7-binding sites by ChIP-seq in differentiating OLs has shown that they are predominantly located in the region +5 kbp relative to a transcription start site of target genes and serve as binding sites for transcription factor Olig2, which is known to regulate enhancers that are functionally important for oligodendrogenesis, in particular, by recruiting Brg1 to them (Yu et al, 2013; He et al, 2016)
The activation of some genes and the repression of others are implemented by precisely spatially and temporally coordinated interactions of various transcription factors with the promoters and enhan cers of these genes. Such fine regulation is possible due to the coordinated fine-tuned work of transcription factors and ATP-dependent chromatin-remodeling complexes, which determine the regulatory landscape of chromatin and contribute to its epigenetic modifications (Copray et al, 2009)

Summary

Introduction

In the research on the workings of the brain, the central role in the functioning of the central nervous system has been assigned to neurons, and various pathological conditions have been regarded as a result of impaired functioning of neurons. When going through the stages of specification, migration, proliferation, and differentiation, OLs undergo dramatic changes in the pattern of gene expression, which require a precisely (temporally and spatially) coordinated interaction of various transcription factors and epigenetic events that determine the regulatory landscape of chromatin (Copray et al, 2009).

Results

Conclusion