Epigenetic regulation of cell identity (Team M. Weber)
Epigenetic modifications of chromatin influence gene expression and play many roles in the regulation of the genome. The establishment of these epigenetic programs is crucial during embryogenesis to establish cell identity, and its stability is essential to maintain the function of the cell types that make up the tissues of the body. The instability and deregulation of epigenetic pathways contribute to the emergence of many human pathologies, in particular cancers.
Our team is particularly interested in DNA methylation, a chemical mark of cytosines catalyzed by the enzymes of the DNA-methyltransferase family: DNMT1, DNMT3a and DNMT3b. In mammals, methylation of cytosines occurs mainly at the level of CpG dinucleotides and can induce stable repression of transcription. DNA methylation has important regulatory functions during development and its deregulation contributes to tumor progression.
Our goals are to better understand the roles of DNA methylation in genome integrity and cell identity, and to identify molecular factors that reshape DNA methylation profiles in mammalian cells. To answer these questions, we use genome-wide epigenome analysis by high-throughput sequencing in combination with bioinformatics, molecular biology and functional genetics.
Role of DNA methylation during mammalian development. We use large-scale epigenome mapping approaches by high-throughput sequencing to study the reprogramming and target sequences of DNA methylation during development. In addition, we use functional approaches and mouse models knock-out for Dnmt genes to test the mechanisms of action of DNA methylation. This work leads to a better understanding of the importance of DNA methylation for the regulation of the transcriptome and the maintenance of cell identity in development.
Study of factors that shape DNA methylation patterns in normal and cancer cells. We wish to understand the molecular mechanisms that reshape genomic DNA methylation profiles during embryonic and tumor development in mammals. To this end, we are conducting functional studies on several candidate factors by genetic inactivation in mice. In addition, we are developing biological and bioinformatic screening projects to identify new epigenetic regulators of DNA methylation in normal and cancer cells. In the long term, this work makes it possible to formulate hypotheses about the mechanisms of abnormal targeting of DNA methylation in cancer cells and to identify new molecular targets for the development of epigenetic therapies for cancer.