Epigenetics, chromatin and brain development and function

Abstract

Research investigating epigenetics and chromatin function in brain and behaviour has mushroomed over the last two decades. And yet epigenetics as a biological concept predates the discovery in the 1950s of DNA as the principle mode of inheritance by over a decade. This review explores the past, present and future research into epigenetics as it relates to understanding brain development and function.

Keywords: DNA methylation; epigenome editing; genomic imprinting; histones; memory; single cell.

Figure 1.

Schematic showing a representative imprinted gene cluster, in this case, the Angelman and Prader–Willi Syndrome (AS/PWS) imprinted cluster on human chromosome 15. As is common for imprinted genes, within this cluster are both maternally (red arrows) and paternally (blue arrows) expressed genes, including a long non-coding RNA (Lnc-RNA). Also marked with black ‘lollipops’ is the differentially methylated region (DMR), which in the case of the AS/PWS locus is methylated on the maternally derived chromosome and un-methylated on the paternal chromosome. The parental-specific marking of the DMR distinguishes the maternal and paternal chromosomes at this interval and guides parental-specific gene expression control via chromatin changes and non-coding RNA (e.g. UBE3A antisense, UBE3A-as).

Figure 2.

Schematic illustrating the possible future applications of single-cell epigenomics to neuroscience. The example here links single-cell electrophysiological recordings with single-cell transcriptomics, genomics and epigenomics. For instance, this would enable a true readout of the gene expression and associated DNA-me and/or chromatin changes that underpin synaptic plasticity.