Basic modes of epigenetic regulation implicated in adult neurogenesis. (a) To initiate epigenetic processes, extracellular and intracellular signals may trigger epigenetic ‘perpetuators’ that form self-sustaining feedback loops or intrinsically produce long-lasting cellular effects in the absence of the initial trigger stimuli. Typical mechanisms by which this process occurs include transcription regulator and non-coding RNA–mediated feedback pathways, DNA methylation with associated methyl-binding proteins (MBDs), and histone H3K27 methylation with associated PcG (polycomb group) and TrxG (trithorax group) complexes. (b) DNA modifications. DNA methyltransferases (DNMTs) catalyze DNA methylation, whereas the pathway leading to DNA demethylation might include 5-methylcytosine (5mC) hydroxylase TET (ten-eleven translocation-1) proteins and DNA excision repair enzymes that are regulated by Gadd45 (growth arrest and DNA-damage-inducible) family proteins. (c) Histone modifications. Specific amino acid residues of histone N-terminal tails can be reversibly modified with a variety of ‘tags’ including acetylation (ac), phosphorylation (p), methylation (me), ubiquitination (ub), SUMOylation (su) and isomerization (iso). The varying turnover rates and biological interpreters of these modifications might execute different cellular functions for epigenetic regulation. C, cytosine; 5mC, 5-methylcytosines; 5hmC, 5-hydroxymethylcytosine; BER, base-excision repair; NER, nucleotide-excision repair; K, lysine; S, serine; T, threonine; R, arginine; P, proline; KAT, lysine acetyltransferase; HDAC, histone deacetylase; KMT, lysine methyltransferase; KDM, lysine deacetylase; PRMT, protein arginine methyltransferase; PADI4, peptidyl arginine deiminase type IV; JMJD6, Fe(II) and 2-oxoglutarate–dependent dioxygenase Jumonji domain-6 protein; DUB, deubiquitinase; SENP, sentrin-specific protease.