Fig. 19.1.

Role of epigenetic mechanisms in gene transcription. Epigenetic mechanisms play central roles in gene regulation mediated by transcription factors (TF) by maintaining active (euchromatin) or repressed (heterochromatin) states of chromatin. These include DNA methylation (DNAMe) and histone post translational modifications (PTMs). In the repressed state, chromatin at repressed genes can be enriched with DNAMe [mediated by DNA methyl transferases (DNMTs)] and repressive histone PTMs such H3K9 methylation (H3K9me), H3K27me and H4K20me mediated by histone methyltransferases (HMTs) SUV39H1, Ezh2 and SUV420H2 respectively. In active states, chromatin is enriched by H3K acetylation (H3KAc) and H4KAc, and H3K4me and H3K36me. Histone acetyltransferases (HAT) such as CBP/p300 and SRC-1 mediate acetylation, while H3K4me is catalyzed by HMTs such as SET7 and MLL family members. Actions of HATs are opposed by histone deacetylases (HDAC). Actions of HMTs are countered by histone demethylases (HDM) such as LSD1 and JARID, which erase H3K4me marks and the JMJD family members, which erase H3K9me and H3K27me marks. This results in gene repression or activation depending on the modification that has been erased. Environmental factors and extracellular signals can affect epigenetic states to modulate the expression of genes associated with various diseases including cancer and diabetes. Ac-lysine acetylation; Me: lysine methylation