Epigenetic enzymes

Epigenetic enzymes are a broad class of proteins responsible for the post-translational modification of histones and the covalent modification of DNA, which collectively regulate gene expression without altering the underlying genetic code [3, 5, 21]. These enzymes are functionally classified into "writers" that add chemical marks (e.g., DNA methyltransferases and histone acetyltransferases), "erasers" that remove them (e.g., histone deacetylases and demethylases), and "readers" that recognize and bind to these modifications to recruit transcriptional machinery [4, 15, 24]. Dysregulation of these enzymes is a critical driver in many diseases, most notably cancer, where aberrant epigenetic landscapes lead to the silencing of tumor suppressor genes and the activation of oncogenes [5, 18, 24]. Therapeutic strategies targeting epigenetic enzymes, such as HDAC and DNMT inhibitors, have been successfully approved for hematological malignancies like cutaneous T-cell lymphoma and myelodysplastic syndromes [8, 11, 15]. Despite their clinical utility, these agents often face challenges related to low specificity and systemic toxicity, including significant hematological and cardiovascular side effects, necessitating the development of more selective, next-generation inhibitors [1, 8, 14]. Beyond oncology, epigenetic enzymes are being explored as targets for neurodegenerative, cardiovascular, and metabolic disorders [10, 13, 23].

Other names

Epigenetic modifiersChromatin-modifying enzymesWritersErasersReaders

Epigenetic drugs primarily function by inhibiting the enzymes responsible for adding or removing chemical marks on DNA and histones, such as DNA methyltransferase (DNMT) inhibition, histone deacetylase (HDAC) inhibition, and histone methyltransferase (HMT) inhibition, thereby restoring normal gene expression patterns [2, 3, 5].