Chromatin modifications, at the level of either histones or cytosines present in DNA, are fundamental regulators of gene expression in eukaryotes as they control the access of the transcriptional machinery to the targeted promoter regions. When these modifications are transmitted during mitosis, they reprogram the daughter cells without altering the genomic sequence, a process termed « epigenetic ». Recent studies have found that chromatin modifications are induced by bacterial pathogens to interfere with the host transcriptional program. However, the mechanisms at play are poorly characterized. Our project is centered on this new facet of host-pathogen interactions. In line with our published work, we will study the chromatin modifications induced by the intracellular bacterial pathogen Listeria monocytogenes, for which we have identified and gathered preliminary data on several factors targeting chromatin. These factors act by two different strategies: - through activation of specific signalling cascades; - through direct control of chromatin regulators. In this project, we plan to elucidate the molecular basis of these new mechanisms by characterizing bacterial proteins, host factors, chromatin marks and genes reprogrammed. Furthermore, we will determine whether DNA methylation or histone modification profiles imposed by bacterial factors are maintained over time, as chromatin modifications (and parallel gene expression) may be transmitted to daughter cells during cell division. This would imply that an infection leaves an epigenetic mark after pathogen eradication, establishing a memory of infection in parallel to acquired immunity. Besides direct obvious implications of such a discovery on public health, it could shed light on possible mechanisms at play in the etiology of certain unexplained affections, such as autoimmune diseases or certain cancers, via bacterial-mediated epigenetic dysregulation of immune responses. To achieve the goals proposed in this project, we will use cutting-edge technologies, such as chromatin/methyl DNA immunoprecipitation followed by deep sequencing, RNAi screening, tandem affinity purification of chromatin complexes and X-ray crystallography. In addition, this project will greatly benefit from the complementary expertise of the four teams involved (microbiology, cellular biology, genomics, epigenetics/chromatin biochemistry and structural biology), the high quality of the infrastructures, and the numerous tools (stable cell lines, bacterial mutants, purified proteins, knock-out mice), which will guarantee advances in the field. All the elements converge for the success of this project.