Understanding the spatial organisation of replicated human chromosomes

Flavia Corsi (IMBA, Vienna)

Apr 13. 2021, 15:50 — 16:15

The three-dimensional organisation of the genome plays a key role in regulating essential cellular functions, including gene expression, DNA repair, recombination, and chromosome segregation during mitosis. Misregulation of chromosome conformations has been associated with developmental disorders, aneuploidy, and cancer. Thus, it is of paramount importance to understand the principles that govern inter- and intra-chromosomal interactions.

The development of high-throughput chromosome conformation capture (Hi-C) technology represented a breakthrough in understanding the internal organisation of chromosomes. How this complex organisation is achieved can be well explained by the loop extrusion model, which proposes dynamic loop formation along the chromosome sequences during the cell cycle. By contrast, interactions between sister chromatids (pairs of replicated chromosomes) and their coordination with intra-chromosome interactions remain poorly understood. The reason was the difficulty to distinguish them, due to their identical DNA sequences. The recent development of the sister-chromatid-sensitive Hi-C (scsHi-C) technique finally enables genome-wide analysis of interactions between sister chromatid sequences. With this new tool at hand, what is missing is the development of theoretical models providing general principles to explain scsHi-C data, and to unravel the mechanisms underlying sister chromatid interactions. The predictions of such models could in turn guide future experimental studies. 

In this talk, I will briefly review the current knowledge on chromosome organisation. Next, I will introduce the major findings of scsHi-C data analyses, and explain the main difficulties posed by their interpretation and modeling. I will then outline the approach we are currently working on to model the structure and the mechanisms of sister chromatids organisation. Finally, I will present some preliminary results and open questions. 

Further Information
Venue:
Erwin Schrödinger Institute - virtual
Recordings:
Recording
Associated Event:
Interdisciplinary Challenges in Nonequilibrium Physics (Online Workshop)
Organizer(s):
Demian Levis (U Barcelona)
Emanuele Locatelli (U of Vienna)
Jan Smrek (U of Vienna)
Francesco Turci (U Bristol)