DNA Methyltransferases: From Evolution to Clinical Applications

Abstract

DNA methylation is an epigenetic mark that living beings have used in different environments. The MTases family catalyzes DNA methylation. This process is conserved from archaea to eukaryotes, from fertilization to every stage of development, and from the early stages of cancer to metastasis. The family of DNMTs has been classified into DNMT1, DNMT2, and DNMT3. Each DNMT has been duplicated or deleted, having consequences on DNMT structure and cellular function, resulting in a conserved evolutionary reaction of DNA methylation. DNMTs are conserved in the five kingdoms of life: bacteria, protists, fungi, plants, and animals. The importance of DNMTs in whether methylate or not has a historical adaptation that in mammals has been discovered in complex regulatory mechanisms to develop another padlock to genomic insurance stability. The regulatory mechanisms that control DNMTs expression are involved in a diversity of cell phenotypes and are associated with pathologies transcription deregulation. This work focused on DNA methyltransferases, their biology, functions, and new inhibitory mechanisms reported. We also discuss different approaches to inhibit DNMTs, the use of non-coding RNAs and nucleoside chemical compounds in recent studies, and their importance in biological, clinical, and industry research.

Chromatin Remodeling-Related PRDM1 Increases Stomach Cancer Proliferation and Is Counteracted by Bromodomain Inhibitor

“…These factors are mainly from families including DNA methyltransferase (DNMT), histone deacetylase (HDAC), PRDM, and protein arginine methyltransferase (PRMT). DNMTs control the methylation of DNA [ 55 ], and HDACs regulate the deacetylation of protein [ 56 ]. PRDMs manipulate gene transcription [ 57 ] while PRMTs control methylation on arginine [ 58 ].…”

Research progress and applications of epigenetic biomarkers in cancer

“…Non-nucleoside inhibitors do not contain the cytosine nucleoside skeleton structure and can bind directly to methylated regions in DNMT, rendering the enzyme ineffective (Del Castillo Falconi et al, 2022). Procaine is a benzoic acid compound with local anesthetic and anti-arrhythmic activity, but it has been found to inhibit the growth and demethylate liver cancer cells by treating them (Tada et al, 2007).…”

Intergenerational Perioperative Neurocognitive Disorder

“…DNMT3a and DNMT3b can establish a new methylation pattern by methylating unmodified DNA, i.e., they function as de novo DNMTs. DNMT1 recognizes hemimethylated DNA formed during replication and copies the original DNA methylation pattern onto the newly synthesized daughter strand (maintenance DNMT) [ 301 , 303 , 304 , 305 , 306 ]. 5mC can be oxidized into 5-hydroxymethylcytosine (5-hmC) by ten-eleven translocation (TET) enzymes.…”