Mechanisms and dynamics of heterochromatin formation during mammalian development: closed paths and open questions

Early embryonic development in mammals is characterized by major changes in the components of the chromatin and its remodeling. The embryonic chromatin and the nuclear organization in the mouse preimplantation embryo display particular features that are dramatically different from somatic cells. These include the highly specific organization of the pericentromeric heterochromatin within the nucleus and the suggested lack of conventional heterochromatin. We postulate that the plasticity of the cells in the early embryo relies on the distinctive heterochromatin features that prevail during early embryogenesis. Here, we review some of these features and discuss recent findings on the mechanisms driving heterochromatin formation after fertilization, in particular, the emerging role of RNA as a regulator of heterochromatic loci also in mammals. Finally, we believe that there are at least three major avenues that should be addressed in the coming years: (i) Is heterochromatin a driving force in development? (ii) Does it have a role in lineage allocation? (iii) How can heterochromatin "regulate" epigenetic reprogramming?