Pierre-Antoine Defossez’s work concerns the mechanisms of transcriptional silencing and the role of DNA methylation in mammals. His group discovered several novel mammalian proteins that recognize methylated DNA and he is characterizing their role in silencing during development and pathologies.

DNA methylation is, by nature, an epigenetic mark: it is borne by the DNA molecule without affecting its sequence, can be reproduced after each cell division, and can influence the activity of the genome. In higher eukaryotes, DNA methylation plays some vital roles in the control of gene expression and genome stability. Our work focuses on DNA methylation in mammals. More specifically, we investigate the proteins that recognize methylated DNA and carry out its biological effects.

One line of investigations aims at characterizing two new human transcription factors that we recently showed to bind methylated DNA. One of these proteins, in particular, presents strong links to cancer, and might serve as a DNA methylation sensor for the cell. Our other, broader line of investigation, aims at the exhaustive identification of human proteins that bind methylated DNA. For this we use in silico approaches, as well as a new genetic approach that we have developed to this end.