19 novembre

Cancer evolution through chromatin plasticity

Le 19 novembre - 09h-11h
Centre de recherche - Paris - Amphithéâtre Hélène Martel-Massignac (BDD)
11 rue Pierre et Marie Curie - 75005 Paris

A key paradigm in biology is that structure determines function. However, to what extent this holds true for the 3D organization of the chromatin in the nucleus remains an open question. High-throughput chromosome conformation capture technologies (Hi-C) have allowed to characterize chromatin 3D architectures and structural elements. Recent evidence has showed that chromatin compartments and sub-compartments are less conserved across cell types than topological domains (TADs). However, inference of chromatin sub-compartments has been limited by data resolution and these structural elements have been characterized only in a handful of cell lines. In this talk, I will present new computational approaches developed in our group that allowed to infer and compare chromatin sub-compartments and compartment domains in >100 cell lines, at variable data resolution. We showed genomic regions undergoing subcompartment repositioning during lineage differentiation and oncogenic transformation. In cancer, subcompartment repositioning was associated with epigenetic reprogramming of histone modifications and driven by mutations of chromatin remodeling factors, hyper-acetylation of clusters of enhancers, and cell plasticity trajectories leading to de- and trans-differentiation. In the final part of my talk, I will discuss in more detail how chromatin plasticity associated with genetic alterations can drive oncogenic transformation of normal cells and promote tumor evolution. Overall, new technologies and computational models to study chromatin 3D architectures can offer a fresh perspective to understand the cancer genome.

Computational Biology & Cancer Genomics group Leader
Invité(es) par
CBIGC groupe Leader (U900)
Institut Curie