CARELL GROUP Research – Epigenetics

Gene Regulation through Chemical Transformation of DNA

In 2009, the presence of the base 5-hydroxymethylcytosine (hmdC) was confirmed in DNA isolated from brain and stem cells.

Tet-enzymes were discovered that generate hmdC from 5-methylcytidine (mdC). This discovery extended the number of known bases in our genome from five (dA, dC, mdC, dG, dT) to six (dA, dC, mdC, hmdC, dG, dT).

The Carell group developed synthetic routes to the new DNA bases and phosphoramidite building blocks together with solid-phase synthesis procedures to enable synthesis of DNA containing the novel bases.

In 2011, we discovered the 7th base of the genome 5-formylcytidine (fdC), and shortly thereafter we found that the Tet enzymes oxidize also dT to hmdU.

Recently we could provide evidence that fdC is directly deformylated to dC in stem cells. This establishes a new potential avenue to active demethylation. These findings have the potential to change the view of how the genetic system is operating.

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