Spatial organisation in the nucleus is not random and it has a role in genome regulation. Large blocks of heterochromatin accumulate at the nuclear envelope and positioning of genes at the nuclear periphery correlates with gene repression. However, this organisation is not fixed and nuclear reorganisation has been described during mammalian development. In the inner cell mass of the blastocyst, chromatin exists in an unusual configuration with apparently widely dispersed open chromatin fibres. Following implantation at the epiblast stage, several hundreds of genes relocate to the nuclear periphery, concomitant with the formation of large domains of heterochromatin there. Interestingly, in the same time, specific genes can also remove from the nuclear envelope to the centre of the nucleus which is associated to their activation. Subsequently, lineage-dependant changes occur during the next steps of development. However, the molecular mechanisms which control this reorganisation are not understood.
Prevailing models assume some transacting factors are responsible for an active recruitment and tethering of specific domains to the nuclear envelope. Thus, I propose, using a candidate approach and a RNAi screen, to identify factors responsible for the nuclear reorganisation observed in EpiSCs and to also address an alternative hypothesis that I have proposed and which involves a more passive accumulation of heterochromatin at the nuclear periphery that is influenced by nuclear pore complexes.