Fig. 3. Modes of epigenetic regulation.

(A) DNA methylation. Methylation of cytosine at position 5 is carried out by DNMTs (DNMT1, DNMT3a and DNMT3b), and inactivation of this methyl group by hydroxymethylation is carried out by the TET enzymes. Names in blue color indicate repression and red color indicates activation of gene expression. (B) Histone PTMs. Only the PTMs catalyzed by the PcG and TrxG complexes (methylation, ubiquitination) or associated (acetylation) with TrxG-dependent PTMs are shown. Histone PTM in blue = PTM associated with gene repression; histone PTM in red = PTM associated with gene activation. (C) miRNAs. The pathway leading to miRNA production is outlined and the fact that miRNAs silence mRNA expression by inducing either mRNA degradation or translational repression is emphasized. (D) Long intergenic noncoding RNAs. Two mechanisms of lincRNA action are depicted. In one of them, lincRNAs modify gene expression by serving as landing pads for transcription factors that either repress or activate transcription. The other mechanism consists of lincRNAs directing the organization of chromatin states to specific genomic regions involved in gene regulation. DNMTs = DNA methyltransferases, TETs = ten eleven translocation (dioxygenase) enzymes; H = histone; Pasha = nuclear protein that is part of the microprocessor complex required for miRNA processing. Pasha associates with the RNA III enzyme Drosha. Drosha = RNA III enzyme that cleaves pri-miRNA (the primary transcript of miRNAs) to precursor (pre)-miRNA, which contains a stem-loop structure; Dicer = endoribonuclease that cleaves pre-miRNA into 20–25 mer double-stranded miRNAs; TRBP = human immunodeficiency virus transactivating response RNA-binding protein; it recruits Dicer to Ago2 for miRNA processing; Ago2 = Argonaut 2, the catalytic component of RISC; RISC = RNA induced silencing complex; Pol II = RNA polymerase 2; TF = transcription factor; CRC = chromatin remodeling complex.