In eukaryotic cells, how chromatin and epigenetic marks are imposed, inherited and/or changed is a central issue for cellular functions and cell fate maintenance. Understanding the logic behind their dynamics is of critical importance to determine the molecular mechanisms behind the maintenance of cellular functions, changes during cell differentiation, and how this can go awry during disease onset and progression. In the CELLECTCHIP proposal, we aim at characterizing dynamics of histone variants and histone post-translational modification (PTMs) marks genome wide in three contexts: establishment, maintenance and erasure. We will exploit two biological situations during which chromatin organization and chromatin marks are remodeled by dynamic mechanisms, but with two distinct outcomes: (i) the dynamics of chromatin marks during S-phase of somatic cell lines for maintenance and (ii) paternal X-chromosome inactivation and reactivation during early mouse development for change. We will develop novel ChIP-seq technologies based on microfluidics and single-cell DNA barcoding that enables ChIP-Seq from very few cells (hundreds) as well as an ability to discriminate post-sequencing the sequence reads originating from individual cells. We will combine these technologies with engineered biological systems allowing the discrimination of (1) parental from newly assembled nucleosomes at defined times time during S-phase progression and (2) paternal X expressing and non-expressing cells from mouse pre-implantation embryos. This proposal should advance the scientific field of epigenetics in an original way (1) by bringing analysis to the level of individual cells and (2) by going beyond a static description of the chromatin/epigenetic landscape since it aims at deciphering the dynamics of histone variants and histone PTMs at particular times in the cell cycle (S-phase) and during development. This dynamic view should contribute to our understanding of epigenetic mechanisms at an unprecedented level and enable development of new technologies in epigenetics for drug discovery and personalized medicine.