Experimental approaches to the study of epigenomic dysregulation in ageing

Abstract

In this review, we describe how normal ageing may involve the acquisition of epigenetic errors over time, akin to the accumulation of genetic mutations with ageing. We describe how such experiments are currently performed, their limitations technically and analytically and their application to ageing research.

Figure 1

Cytosine methylation can be studied a number of ways, but the assays mostly fall into the three categories shown. Restriction enzymes can selectively digest unmethylated or methylated DNA, affinity reagents can also bind selectively to each methylation state, while chemical mutagenesis with sodium bisulphite preferentially deaminates unmethylated cytosine to generate uracil, with methylcytosine being relatively protected. In all cases it becomes necessary to map the products of the initial enrichment, selection or chemical conversion to determine where in the genome the methylated cytosines are located, usually involving microarrays or massively-parallel sequencing.

Figure 2

Four post-translational modifications of specific amino acids of the linker (H1) or core histones are illustrated to demonstrate the potential combinatorial complexity that they confer.