Fig. 1
Major epigenetic mechanisms of transcriptional regulation. Multiple epigenetic modifications regulate transcription. DNA methylation, which is catalyzed by DNA methyltransferases (DNMTs) and reversed by Tet methylcytosine dioxygenases (TETs), typically represses transcription by impairing transcription factor (TF) binding. In contrast, histone posttranslational modifications (PTMs), including acetylation, methylation, and ubiquitination, modulate chromatin structure and transcriptional accessibility. Histone acetylation is regulated by histone acetyltransferases (HATs) and histone deacetylases (HDACs), and promotes gene expression by opening chromatin. In contrast, the methylation of specific histone residues, which is regulated by lysine histone methylases (KTMs) and lysine demethylases (KDMs), has functional consequences that are influenced by the position of the residue and the degree of methylation. Similarly, histone ubiquitination, which is catalyzed by E1-activating-E2 conjugating-E3 ligase systems, including polycomb repressive complex 1 (PRC1), and is reversed by deubiquitinating enzymes (DUBs), with histone 2A (H2A) and H2B as the main targets, regulates gene expression in a context-dependent manner. Notably, these marks not only affect local promoter activity but also regulate distal elements such as enhancers. Moreover, epigenetic modifications often act in concert, with extensive crosstalk between DNA methylation and histone PTMs, either synergistically or antagonistically influencing gene expression, partly through the recruitment of reader proteins and chromatin remodeling complexes
