Selective and catalytic conversion of hydroxymethyl cytosine into formyl cytosine using a synthetic model of TET enzymes

Abstract

TET enzymes, known as the ten–eleven translocation enzymes, have become central figures in epigenetic regulation due to their remarkable ability to oxidize 5-methylcytosine (5-mC) to 5-hydroxymethylcytosine (5-hmC), 5-formylcytosine (5-fC), and 5-carboxycytosine (5-caC), thus influencing gene expression and DNA methylation patterns. Understanding the intricate mechanisms underlying TET enzyme function is crucial for unraveling epigenetic regulatory pathways and their implications in various biological processes, including development, differentiation, and disease progression. Recently, we have shown that the Fe^IIITAML complex acts as a synthetic model of TET enzyme by selectively oxidizing 5-hmC to 5-fC. Herein, we report another synthetic model, Fe^IIIbTAML, for selective and catalytic oxidation of 5-hmC. The current synthetic model overcomes several limitations of the previous TET model reported by us. In addition to oxidizing a simple nucleobase, we have shown that Fe^IIIbTAML, in the presence of H₂O₂, can selectively oxidize nucleosides and small DNA fragments containing 5-hmC in a catalytic manner.