IBEC Seminar: Marc Martí-Renom

Structure determination of genomes and genomic domains by satisfaction of spatial restraints

The genome three-dimensional (3D) organization plays important, yet poorly understood roles in gene regulation. Chromosomes assume multiple distinct conformations in relation to the expression status of resident genes and undergo dramatic alterations in higher order structure through the cell cycle. Despite advances in microscopy, a general technique to determine the 3D conformation of chromatin has been lacking. We developed a new method for the determination of the 3D conformation of chromatin domains in the interphase nucleus, which combines 3C-based experiments with the computational Integrative Modeling Platform (IMP). The general approach of our method, which has been applied to study the 3D conformation of the alpha-globin domain in the human genome [1], the Caulobacter crescentus whole genome [2], and the dynamic response of Topologically Associating Domains (TADs) to hormone treatment in breast cancer cell lines [3], opens the field for comprehensive studies of the 3D conformation of chromosomal domains and contributes to a more complete characterization of genome regulation.
[1] D. Baù et al. Nat Struct Mol Biol (2011) 18:107.
[2] M.A. Umbarger, et al. Molecular Cell (2011) 44:252
[3] Le Dily, et al. Genes & Dev (2014) 28:2151

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