Unraveling the structure of paired homologs and sister chromatids with Hi-C and polymer modeling
The genomes of living organisms are stored on DNA molecules, called chromosomes, which are typically present in multiple copies. For example, diploid organisms have two slightly different copies of each chromosome, called homologs. Moreover, in preparation for division, cells duplicate their chromosomes, thus producing two identical sister chromatids. Sister chromatids and, in some contexts, homologs must stay aligned in close proximity to facilitate several biological functions, particularly, DNA repair and recombination. Yet, until recently, our understanding of the mutual positioning of chromatids and homologs remained very coarse-grained, due to the low resolution and throughput of available experimental methods.
In my talk, I will demonstrate that sequencing-based methods called Chromosome Conformation Capture (a.k.a. Hi-C) can yield a high-resolution picture of physical interactions between homologs and sister chromatids. First, I will show how Hi-C can be used to study the structure of aligned homologs in Drosophila flies. Second, I will show how a modification of Hi-C can reveal the map of physical interactions between sister chromatids in human cells. I will use these two case studies to illustrate the strengths and current limitations of Hi-C-based approaches to chromosome structure determination. In conclusion, I will talk about our ongoing effects to infer the structure and biological mechanisms of chromosome pairing by means of physics-based modeling.
IMBA Vienna, Austria