Epigenetics and Development
In mammals, DNA is wrapped in a higher order structure called “chromatin” and is therefore not readily accessible. To overcome the impediment imposed by this structure, cells have evolved “epigenetic” mechanisms, such as DNA methylation, that can change the chromatin configuration without affecting the DNA sequence. Interestingly, DNA-binding factors seem to exclusively occupy regions of low DNA methylation levels. However, how DNA methylation affects the recruitment of DNA-binding factors is currently poorly understood. DNA-binding factors can be divided into two types: factors that bind to DNA in a sequence-specific fashion, such as transcription factors and factors that bind in a sequence-independent fashion, such as DNA damage response (DDR) factors.
We are interested in studying the effect of DNA methylation on the recruitment of both types of DNA-binding factors on one hand, and the consequence of the recruitment of these factors on DNA methylation and the chromatin structure on the other hand. The outcome of our studies will shed light on the implication of the aberrant distribution of DNA methylation observed in cancer cells, in the generation of defects in transcription regulation and DDR in these cells.
Our experimental approach is based on the use of Next Generation technologies for Sequencing (ChIP-Seq, Bis-Seq, RNA-Seq), Proteomics, and "Genome Editing" (CRISPR-Cas9). As cellular models, we are using mouse Embryonic Stem Cells (ESCs) and human cancer cell lines.