Chromatin 3D organization and regulation of transcription

The three-dimensional (3D) organization of chromatin within the cell nucleus is crucial for regulating genome functionality. The knowledge of its role has greatly advanced thanks to the development of novel imaging and molecular biology techniques. In particular, chromosome conformation capture (3C) and its high-throughput derivatives, based on next generation sequencing, allow investigating chromatin architecture on a genome-wide scale.

My research group is focused on the use of 3D chromatin organization data to gain mechanistic insights into transcription and epigenetic regulation at different levels.

On a large scale, we investigate mechanisms for the coordinated regulation of large chromatin domains in physiological and disease conditions. These involve, for example, the organization of the genome in distinct structural domains, such as Topologically Associating Domains (TADs), or Lamina Associated Domains (LADs).

On a finer scale, instead, we study distal regulatory elements (enhancers) and their epigenetic or genetic alterations in genetics diseases and cancer. In this context, we leverage chromatin 3D organization data to refine the association of distal regulatory elements and their target genes, to characterize the functional role of enhancers in epigenetics and gene expression regulation, within the broader gene regulatory network.

I will discuss recent work from my lab and in particular how the development of specific computational biology solutions has been instrumental to address unanswered biological questions.