During cell differentiation or metabolic switch, cells undergo profound changes in gene expression. These events are accompanied by complex modifications of chromosomal components and nuclear structures, including covalent modifications of DNA and chromatin up to topological reorganization of chromosomes and genes in the nucleus. To various extents, all these levels of organization appear to contribute to the stability and heritability of transcription programmes and define what is meant as the epigenomic level of gene regulation. Indeed, damage or perturbation of epigenome components may lead to deviations from a determined cellular programme, resulting in severe developmental disorders and tumour progression. Most recent data also suggest that tissue regeneration and transdifferentiation are controlled by epigenetic functions. Thus, the epigenome provides the molecular basis for the preservation and also for the plasticity of cell identity.