Description:

The Simpson Querrey Institute for Epigenetics presents:

Giacomo Cavalli, PhD

Director, Chromatin and Cell Biology Lab, Institute of Human Genetics, Université de Montpellier, France

"The Role of 3D Genome Organization and Polycomb Proteins in Cell Differentation and Development"

The eukaryotic genome folds in 3D in a hierarchy of structures, including nucleosomes, chromatin fibers, loops, chromatin nanodomains, topologically associating domains (TADs), compartments and chromosome territories that are highly organized in order to allow for stable memory as well as for regulatory plasticity, depending on intrinsic cues, such as chromatin association of Polycomb proteins, CTCF and cohesion, and on environmental cues. We showed that TADs and chromatin loops can assist gene regulation, both in Drosophila and in mouse cells. However, the physical nature of compartments, TADs and loops remain elusive and single-cell studies are critically required to understand it. We characterized chromatin folding in single cells using super-resolution microscopy, revealing structural features inaccessible to cell-population analysis. TADs range from condensed and globular objects to stretched conformations. Favored interactions within TADs are regulated by cohesin and CTCF through distinct mechanisms. Furthermore, super-resolution imaging revealed that TADs are subdivided into discrete nanodomains. 

We also analyzed loops that depend on chromatin components that regulate the expression of a large number of genes, dubbed as Polycomb group proteins. Originally, these factors were shown to silence gene expression and we found that they induce the formation of chromatin loops. The disruption of one of these loops reduces silencing of a target genes, suggesting that loops may play instructive roles in gene regulation. Surprisingly, Polycomb components are also involves in chromatin loops linked with transcriptional activation. Furthermore, their chromatin organization ability can induce stable epigenetic memory that can be inherited through cell division and across organismal generations. Our progress in these fields will be discussed.