Three dimensional architecture of human chromosomes: from data analysis to polymer models
Maxim Imakaev, MIT
The three-dimensional and physical organization of genomes within cells plays critical roles in regulating chromosomal processes, including gene regulation, DNA replication, and genome stability. A recently developed method, Hi-C, provides a comprehensive whole-genome information about physical contacts between genomic region. Analysis of these data has begun to reveal determinants of 3D genomic organization.
Chromosomes can be understood as long polymers. We use a combination of data analysis and polymer modelling to pinpoint main determinants of the 3D genomic organization in several studied organisms. We build polymer models based on the known or suggested principles of chromosomal organization and validate them against the Hi-C data. In particular, we have shown that yeast chromosomal organization can be well-described by a star-polymer model. The model we developed is consistent with the yeast Hi-C data, microscopy observations and diffusion measurements of yeast chromosomes.
We also study folding of the human chromosomes during metaphase, which is vital for completion of cell division. Here, polymer modelling allowed us to discriminated between the two long-studied models of metaphase chromosomes: « bottle-brush » model of loops emanating from a central scaffold, and an hierarchical folding principle.