Biotechnology and cell signalling (Jean-Luc Galzi)
(UMR 7242) > Genome integrity and tumor biology (Scientific coordination : Valérie Schreiber) > Epigenetic regulation of cell identity (Michaël Weber) > Research projects > Research projects
Functions of DNA methylation during mammalian development.
DNA methylation profiles are extensively reprogrammed in a cell type specific manner during mammalian embryonic development. However the targets and precise functions of DNA methylation in genome regulation remain elusive. In order to identify the targets and mechanisms of action of DNA methylation, we use genomics approaches and high-throughput sequencing to generate comprehensive genome-scale epigenome maps in human and mouse cell lineages, which is complemented by functional studies and mouse genetic models to test the function of DNA methylation genetically. These projects help us to decipher the roles of DNA methylation in pluripotency and lineage choices.
Identification of targets of promoter DNA methylation during mouse development by Methylated DNA Immunoprecipitation (taken from Borgel et al, 2010, Nature Genetics 42, 1093-10100)
Identification of factors that shape the epigenome.
While most gene promoters remain constitutively unmethylated, a few regulatory sequences are targeted by DNA methylation during embryonic development. Given that DNA methyltransferases don’t have major sequence preferences, how this remarkable specificity is achieved remains one major open question. Several models can be formulated and need to be validated in mammalian cells. The identification of targets of DNA methylation in mammalian genomes puts us in the position to test the role of candidate factors in the recruitment of the DNA methylation machinery. By combining studies with known candidate targeting factors and identification of novel factors, we aim at identifying the mechanisms that shape the DNA methylome during development. This work will serve to formulate novel hypotheses to explain the abnormal targeting of DNA methylation in cancerous cells.