Multiscale 3D Genome Rewiring during Mouse Neural Development

3D genome organization is intimately linked to its biological function. Changes in nuclear architecture can affect cell fate and disruption of genome topology can result in pathological phenotypes. The Cavalli lab has mapped 3D chromatin organization at ultra-high resolution in ES cells and in neuronal progenitors and cortical neurons, differentiated in vitro or sorted from mouse embryonic brain in vivo.

The findings showed that gene activation is correlated with chromatin insulation and long-range interactions, and that highly transcribed, exon-rich genes frequently engage in long-range contacts both in cis- and in trans. Furthermore, an extensive network of cell type-specific regulatory interactions is dynamically reprogrammed during neural differentiation, reshaping Polycomb-repressive networks as well as activating enhancer-promoter interactions. These findings illustrate how 3D nuclear architecture is deeply linked to the normal physiological and pathological function of the brain in vivo.

Bonev, B., Mendelson Cohen, N., Szabo, Q., Fritsch, L., Papadopoulos, G.L., Lubling, Y., Xu, X., Lv, X., Hugnot, J.P., Tanay, A., et al. (2017). Multiscale 3D Genome Rewiring during Mouse Neural Development. Cell 171, 557-572.e524.