PubReading [23] - Deformylation of 5-Formylcytidine in Different Cell Types - E. Korytiakovà and T. Carell

<p><strong>Epigenetic programming</strong> of cells requires methylation of deoxycytidines (dC) to <strong>5-methyl-dC </strong>(mdC) followed by oxidation to 5-hydroxymethyl-dC (hmdC), 5-formyl-dC (fdC), and 5-carboxy-dC (cadC). Subsequent transformation of fdC and cadC back to dC by various pathways establishes a chemical intra-genetic control circle. One of the discussed pathways involves the Tdg-independent <strong>deformylation</strong> of fdC directly to dC. Here we report the synthesis of a <strong>fluorinated</strong> fdC feeding probe (F-fdC) to study direct deformylation to F-dC. The synthesis was performed along a novel pathway that circumvents any F-dC as a reaction intermediate to avoid contamination interference. Feeding of F-fdC and observation of F-dC formation in vivo allowed us to gain insights into the <strong>Tdg-independent</strong> removal process. While deformylation was shown to occur in stem cells, we here provide data that prove deformylation also in different somatic cell types. We also investigated active demethylation in a non-dividing neurogenin-inducible system of <strong>iPS cells</strong> that differentiate into bipolar neurons. - doi.org/10.1002/anie.202107089. - 2021</p>