TETology: Epigenetic Mastermind in Action

Appl Biochem Biotechnol. 2021 Mar 10. doi: 10.1007/s12010-021-03537-5. Online ahead of print.ABSTRACTCytosine methylation is a well-explored epigenetic modification mediated by DNA methyltransferases (DNMTs) which are considered "methylation writers"; cytosine methylation is a reversible process. The process of removal of methyl groups from DNA remained unelucidated until the discovery of ten-eleven translocation (TET) proteins which are now considered "methylation editors." TET proteins are a family of Fe(II) and alpha-ketoglutarate-dependent 5-methyl cytosine dioxygenases-they convert 5-methyl cytosine to 5-hydroxymethyl cytosine, and to further oxidized derivatives. In humans, there are three TET paralogs with tissue-specific expression, namely TET1, TET2, and TET3. Among the TETs, TET2 is highly expressed in hematopoietic stem cells where it plays a pleiotropic role. The paralogs also differ in their structure and DNA binding. TET2 lacks the CXXC domain which mediates DNA binding in the other paralogs; thus, TET2 requires interactions with other proteins containing DNA-binding domains for effectively binding to DNA to bring about the catalysis. In addition to its role as methylation editor of DNA, TET2 also serves as methylation editor of RNA. Thus, TET2 is involved in epigenetics as well as epitranscriptomics. TET2 mutations have been found in various malignant hematological disorders like acute myeloid leukemia, and non-malignant hematological disorders like myelodyspla...
Source: Applied Biochemistry and Biotechnology - Category: Biochemistry Authors: Source Type: research