Varied Ensembles of Long-range ChROmatin interactions drive chromatin compartmentalization
Yogesh Ostwal, Fernando Muzzopappa, Alexandre Heurteau, Raoul Raffel, Alaguraj Veluchamy, Karthik Eswara, Ahlem Boudellioua, Shakila Ali, Reema Kumari, David Depierre, Satya Vadlamani, Naomi Schickele, Stéphane Schaak, Fabian Erdel, Olivier Cuvier, Wolfgang FischleAbstract
The chromatin components that are involved in organizing eukaryotic genomes into active and inactive compartments remain unclear. In analysing viable Caenorhabditis elegans mutants lacking different chromatin-regulatory proteins, we found that the HP1-type factor HPL-2 and the MBT-domain protein LIN-61 jointly contribute to chromatin compartmentalization. Genomic regions bound by both proteins and their cognate histone mark H3 lysine 9 dimethylation (H3K9me2) form broad interfaces of 30–50 kilobases that engage in combinatorial interactions, which we term ‘Varied Ensembles of Long-range ChROmatin interactions’ (VELCROs). Remarkably, VELCROs are defined by high density of H3K9me2, HPL-2, and LIN-61 sites, but not by the intensity of their individual peaks. Mutants that display defective chromatin compartmentalization are impaired in VELCROs. Polymer simulations show that VELCROs can drive a phase transition that segregates B from A chromatin compartments depending on peak densities. Our work identifies VELCROs as stochastic ensembles of interactions constrained within defined chromatin hubs that shape genome compartmentalization.