Epigenetics in the nervous system

Abstract

It is becoming increasingly clear that epigenetic modifications are critical factors in the regulation of gene expression. With regard to the nervous system, epigenetic alterations play a role in a diverse set of processes and have been implicated in a variety of disorders. Gaining a more complete understanding of the essential components and underlying mechanisms involved in epigenetic regulation could lead to novel treatments for a number of neurological and psychiatric conditions.

Figure 1.

Schematic representation of epigenetic marks. A, DNA is condensed within the nucleus through interactions with histones, and this DNA–protein complex is referred to as chromatin. Two copies each of the histones H2A, H2B, H3, and H4 assemble to form a histone octamer, around which 146 bp of genomic double-stranded DNA are wrapped. B, The N-terminal tail of a histone contains many sites for epigenetic marking via histone acetylation, methylation, and phosphorylation. For example, acetylation of H3, shown as the addition of green circles to the tails, results in a relaxed chromatin state that promotes gene transcription, whereas methylation (shown via red circles) can either promote or repress gene transcription. C, Methylation of DNA is another method of epigenetic marking of the genome, where a methyl group (shown as red diamonds) is transferred to cytosines in genomic regions in and around gene promoters that are rich in cytosine-guanine nucleotides (CpG islands). While the addition of methyl groups at gene promoters is generally linked to transcriptional repression, it is noteworthy that more distal and intragenic portions of many actively transcribed genes are methylated.