Active DNA demethylation at enhancers during embryogenesis

Arne Smits.jpg

In the new issue of Nature Genetics, Arne Smits under supervision of Michiel Vermeulen from the Dept. of Molecular Biology, theme Cancer development and immune defence together with researchers from the Dept. of Molecular Developmental Biology and research groups from Australia and Spain reveal the biochemical mechanism of enhancer activation during vertebrate embryogenesis.

During early embryonic development genes get turned on and off in order to specify the tissues and organs of the developing organism. Whether a gene will be active or not at a given developmental time-point will largely depend on the regulatory regions called enhancers that are located in the vicinity of these genes. Nowadays we know that many human diseases including cancer are linked to aberrancies in enhancer function. In this study, the authors demonstrate that the activation of embryonic enhancers consists of the removal of a chemical mark called the methyl group from the DNA molecule which in turn enables activating proteins to bind those DNA regions. Of particular importance is the fact that this biochemical event takes place during the phylotypic stage, an embryonic phase during which the members of various animal groups look very much alike. This work confirms the existence of such a phase on the level of the DNA sequence and highlights the regulatory complexity of the most evolutionarily conserved stage of vertebrate embryogenesis.


Nature Genetics: Active DNA demethylation at enhancers during the vertebrate phylotypic period, 2016




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