Life Sciences Research for Lifelong Health

Genome re-organisation during nuclear reprogramming

The three-dimensional organisation of a genome has important functions in coordinating gene regulatory networks and orchestrating cellular identity. Pluripotent stem cells 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 are investigating 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 examining the role of pluripotency factors in orchestrating these events. Results could have important implications for understanding the molecular details of reprogramming and for elucidating the mechanistic linkages that exist between nuclear organisation and cell function.

Chromatin

Chromatin is highly dispersed in pluripotent stem cells, whereas somatic cells are characterised by regions of more compact chromatin. Dynamic changes in chromatin architecture can be tracked during stem cell differentiation and reprogramming, thereby providing a useful system to study the mechanisms and functions of chromatin organisation in regulating cell state.