By standing at the crossroads of generations, germ cells ensure species continuity. At the time of fertilization, the oocyte and spermatozoon carry the genetic material but also non-genetically encoded, epigenetic information. Gametic epigenetic modifications have immediate effects on gametic production and fertility. They also have long-term consequences on somatic phenotypes when transmitted to the progeny. Our team has previously made some important contributions to the emergence of these concepts. Here we propose to explore further the epigenetic control of mammalian reproduction, with a specific emphasis on DNA methylation-related events. How are DNA methylation patterns shaped? How do they impact on germ cell identity and integrity? How much gametic DNA methylation is transmitted to the progeny and how does this influence phenotypes across generations?Our projects can be subdivided into three interconnected themes, which are at the heart of mammalian developmental biology and are not usually investigated as a common effort: 1) Trans and cis determinants of de novo DNA methylation, 2) DNA methylation and transposon control, and 3) DNA methylation and genomic imprinting. Our approach is mainly fundamental, using the mouse as a mammalian model, and will involve a powerful combination of genetics, cellular and developmental biology, with large-scale genomic and biochemical strategies. We are also extending our research to humans, in the hope of uncovering new causes of impaired or malignant gametogenesis. Correct DNA methylation patterns are paramount for the generation of functional gametes capable of forming viable and healthy offspring, but also for the regulation of pluripotency states and the maintenance of genome architecture and function in somatic cells. Our work therefore not only impacts on the field of reproduction and development, but also on stem cell biology and cancer.