The role of 3D genome structure in the regulation of gene expression: theoretical tools and models

Annick Lesne
CNRS, IGMM (Montpellier, group of T. Forné) & LPTMC (Paris, M3V team)
Tuesday, january 12, 2016, 2pm, LIRMM Bat5 Salle 1.124

Recent experimental techniques, known as chromosome conformational capture, now give access to the pairwise contacts occurring between genomic loci in living cells. However, the interpretation of the contact frequencies in terms of the 3D spatial structure of the genome is not straightforward.  Both data-driven approaches and model-driven approaches could be considered.
I will first present an algorithm based on distance geometry and graph distance, ShRec3D [1], allowing a very fast  reconstruction and visualization of the 3D genome structure from genome-wide contact maps (the so-called Hi-C data). I will then present how polymer models  could describe the statistical shape of the chromatin fiber,  in different species or different cell types, and give access to its physical parameters (e.g. compaction and rigidity)  from  quantitative data  obtained using the 3C-qPCR technique previously developed by our IGMM group [2,3].  We proposed, based on such 3C-qPCR data for the H19-IgF2 locus, that parental imprinting (i.e. differential DNA methylation of the paternal and maternal alleles)  may control a genetic switch  mediated by a conformational transition of the chromatin fiber [4].

References:
[1] Lesne et al., Nature Methods 11: 1141 (2014)
[2] Court et al.  Genome Biology 12: R42 (2011)
[3] Ea et al.  BMC Genomics,  16: 607 (2015)
[4] Lesne et al. J. Phys. Cond. Mat.  27: 064114  (2015)

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