The general objective of our group is to build quantitative models of the epigenomic-based mechanisms of gene regulation involved in the short- and long-term cellular response. Using theoretical approaches from statistical and numerical physics and in close collaboration with experimentalists, we study the “1D” assembly of the different eu- and heterochromatin states along the genome (nucleation, spreading, compartmentalization and mitotic/meiotic inheritance), and their “3D” folding and nuclear organization. At the nucleosomal and gene scales, we are currently developing molecular models accounting for the combined action of chromatin regulators and DNA binding proteins to understand the mechanisms by which chromatin states achieve their functions. At larger scale, we use coarse-grained models to derive the structural and dynamical properties of the epigenome: (i) the regulation of epigenomic domains (ii) their folding into spatial compartments and (iii) finally the coupling between 3D organization and 1D assembly. Ultimately our goal is to provide a general framework to understand how the epigenome is regulated and how its affect gene expression: from its establishment during development and differentiation to its deregulation in diseases.