Final Report Summary - DNADEMETHYLASE (Functions and mechanism of active DNA demethylation)
Our research has contributed to unravelling this process by studying the role of the tumor suppressor gene Gadd45, a key regulator of DNA demethylation. We have provided evidence that Gadd45 acts as an adapter between genes to be demethylated and the enzymatic machinery carrying out the demethylation. Other central questions regarding Gadd45, which were addressed in the course of this ERC funded project were: What is the biological role of Gadd45? How is Gadd45 targeted to specific sites in the genome? One surprising finding in the course of the ERC funded project was that Gadd45g plays a critical role in mammalian sex determination, because genetically male mice mutant for Gadd45g develop as females. Another surprise was that ribonucleic acids act as a zip code to deliver Gadd45 and hence demethylation to a specific locus. Thus, thanks to ERC support we were able to further unravel the function and biological role of a key player involved in epigenetic regulation.