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Cell Tissue Res (2014) 356:609616
DOI 10.1007/s00441-014-1815-y
REVIEW
Glial epigenetics in neuroinflammation and neurodegeneration
Ori Staszewski & Marco Prinz
Received: 22 November 2013 /Accepted: 14 January 2014 /Published online: 21 March 2014 # Springer-Verlag Berlin Heidelberg 2014
Abstract Epigenetic regulation shapes the differentiation and response to stimuli of all tissues and cells beyond what genetics would dictate. Epigenetic regulation acts through covalent modifications of DNA and histones while leaving the nucleotide code intact. However, these chromatin modifications are known to be vital components of the regulation of cell fate and response. With regards to the central nervous system (CNS), little is known about how epigenetic regulation shapes the function of neural cell types. The focus of research so far has been on epigenetic regulation of neuronal function and the role of epigenetics in tumorigenesis. However, the glial cell compartment, which makes up 90 % of all CNS cells, has so far received scant attention as to how epigenetics shape their differentiation and function. Here, we highlight current knowledge about epigenetic changes in glial cells occurring during CNS injury, neuroinflammatory conditions and neurodegenerative disease. This review offers an overview of the current understanding of epigenetic regulation in glial cells in CNS disease.
Keywords Glia . Epigenetics . Neurodegeneration .
Microglia . Astrocytes . Neuroinflammation
Introduction
Epigenetics as a term was coined in the 1940s by Waddington (1942), originally covering the study of all processes involved in the mechanism by which the genes of the genotype bring
about phenotypic effects. Since then, the field of epigenetics has evolved in scope and the term has acquired a more focused interpretation, now referring to the study of changes in gene function that are mitotically and/or meiotically heritable and that do not entail a change in DNA sequence (Wu 2001). Such changes are effected through covalent chromatin modifications, including modifications of the DNA itself as well as of the histones that are tightly associated with the DNA making up the bulk of the chromatin structure. The most common and best-studied DNA modification is cytosine methylation, which occurs predominantly at CpG residues (Fig. 1; Table 1). Transcriptionally, silenced genes often exhibit strongly methylated CpG-rich regions (CpG islands) in or close to their promoter regions, while transcriptionally active genes typically lack...