S-adenosyl-methionine-dependent DNA and histone methyltransferase pathways (SAM-dependent methyltransferase pathways)

S-adenosyl-methionine-dependent DNA and histone methyltransferase pathways encompass a broad class of enzymes that catalyze the transfer of a methyl group from S-adenosyl-L-methionine (SAM) to DNA or histone proteins. These enzymes, including DNA methyltransferases (DNMTs) and histone methyltransferases (HMTs), are fundamental regulators of the epigenetic landscape, influencing chromatin structure and gene accessibility (Source: PubMed, PMID: 26077081). DNA methylation typically occurs at CpG islands and is associated with long-term gene silencing, while histone methylation can result in either transcriptional activation or repression depending on the specific lysine or arginine residue modified (Source: Nature Reviews Genetics, 2016). Dysregulation of these pathways, such as the overexpression of EZH2 or mutations in DNMT3A, is frequently observed in various cancers, leading to the silencing of tumor suppressor genes and promoting oncogenesis (Source: NIH, National Cancer Institute). Therapeutic strategies targeting these pathways include nucleoside analogs that inhibit DNMTs and small-molecule inhibitors that compete with SAM or the substrate binding sites of HMTs (Source: Journal of Clinical Investigation, 2014). While effective in certain hematological malignancies, challenges remain regarding the specificity of these agents and the potential for global epigenetic toxicity (Source: Frontiers in Cell and Developmental Biology, 2020).

Other names

SAM-dependent methyltransferasesDNA and histone methylation machineryEpigenetic methyltransferase pathwaysS-adenosyl-L-methionine-dependent methyltransferases

Inhibition of methyltransferase enzymatic activity through substrate competition, incorporation into DNA to form covalent complexes with enzymes (trapping), or competitive inhibition at the S-adenosyl-methionine (SAM) binding site (Source: Pharmacology & Therapeutics, 2018).