The organization of single-cell genome into TADs and chromatin nanodomains.

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 Abstract:

Deciphering the rules of genome folding in the cell nucleus is essential to understand its function. Topologically Associating Domains (TADs) represent a new chromosomal entity detectable in interphase nuclei by cell population analysis such as High-throughput Chromosome Conformation Capture (Hi-C). Highly conserved through evolution, TADs partition the genome at the sub-megabase scale and have been proposed to delimit regulatory landscapes where functional interactions between genes and distal cis-regulatory elements may occur. However, the structure of TADs and their association with genome activity in individual cells are still under debate.To investigate the folding of the chromatin fiber at the sub-megabase level in single cell, we have been using Oligopaint FISH probes combined with super-resolution microscopy (3D-SIM). This approach allowed us to better define the physical nature of TADs as well as their correspondence to the epigenetic landscape. I will present our most recent data concerning the folding of chromosome into TADs and nanodomains in both Drosophila and mouse ES cells, and highlight some common and distinct features of genome organization in these organisms.