Varied Ensembles of Long-range ChROmatin interactions drive chromatin compartmentalization
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Updated: Nov 4, 2026

Deciphering High-Resolution 3D Chromatin Organization via Capture Hi-C
Published on: October 14, 2022
Yogesh Ostwal1, Fernando Muzzopappa2, Alexandre Heurteau3
1Bioscience Program, Division of Biomedical Sciences, King Abdullah University of Science and Technology (KAUST), Thuwal 23955-6900, Kingdom of Saudi Arabia.
Abstract:
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.
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