An ambitious EC-funded research initiative on epigenetics advancing towards systems biology

The three-dimensional organisation of a genome has important functions in coordinating gene regulatory networks and orchestrating cellular identity. Pluripotent embryonic stem cells, derived from early embryos or through nuclear reprogramming, have an unusual genome organisation with highly dispersed chromatin fibers and few domains of compacted chromatin. This structural configuration is distinct from more differentiated cell types, which contain regions of compacted chromatin, and suggest that large-scale genome organisation plays a critical role in modulating cell state. We will investigate the process through which global chromatin remodelling occurs during the establishment of pluripotency by identifying genome-wide DNA interactions during nuclear reprogramming of differentiated cells and by developing quantitative models of three-dimensional chromosome organisation. The results will have important implications for understanding the molecular details of reprogramming and for elucidating the mechanistic linkages that exist between nuclear organisation and cell function.