The rapid turnover of DNA cytosine methylation and nucleosomal histones. (A) The turnover rate equation. dC/dt represents the turnover rate of DNA cytosine methylation or nucleosomal histone PTMs, where C is concentration, t is time, k
the synthesis rate, k
the decay rate, and C
the starting concentration. Approximate turnover rates (see text) are estimated from the rate of change in modification levels, when neither k
= 0. Half-life (t
) is the time it takes for a two-fold change in C
. (B) The turnover of DNA 5'-methylcytosine and 5'-hydroxymethylcytosine. The half-life (t
) for 5MeC residues is estimated in hours or less at selected sites. DNA methyltransferases (DNMTs) contribute to synthesis of 5mC from C, the TETs oxidize 5MeC to 5hmC and other products discussed in the text, and the Gadds and TETs contribute to the decay of 5MeC and 5hmC back to C. (C) The turnover of nucleosomal histones and histone PTMs. The half-lives for nucleosomal histones and their PTMs are estimated in tens of minutes or less at selected sites. Nucleosomal histone turnover (left) is catalyzed by chromatin remodeling factors such as SWR1 and ASF1. The turnover of acetylated histone side chains (right) is catalyzed by lysine acetyltransferases (KATs) that add acetyl groups and histone deacetylases (for example, HDACs, SIRT1) that remove acetyl groups. The nucleosome is a symmetrical structure composed of four pairs of histones (large spheres) wrapped in approximately 147 bp of DNA (grey line). DNA dinucleotides that may contribute to nucleosomal positioning and CDI are spaced 10 bp apart (yellow dots). (D) The turnover of chromatin modifications is site specific with rates varying across gene regions, as indicated by the widths of the arrows.