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Degenerate long-range interactions drive phase transition of heterochromatin [Hi-C]

ABSTRACT: Despite intensive efforts, the molecular mechanisms that organize genomes into A and B compartments are still not understood. This is largely due to experimental challenges in targeted manipulation of the molecular components involved. We made use of C. elegans as elementary model system to unveil fundamental concepts of genome compartmentalization. Simultaneous deletion of the H3 lysine 9 methylation-binding proteins HPL-2, a heterochromatin protein 1- type factor, and LIN-61, a malignant brain tudor-domain factor, expression of a dominant negative HPL-2 mutant, or abolishment of H3 lysine 9 methylation resulted in near-complete loss of A/B compartmentalization. Compartmentless genomes follow an equilibrium model of organization with transitions of compartment identity having only moderate effects on local contact domains or on gene expression. We identify degenerate long-range interactions that scalewith the high combined genomic density of HPL-2, LIN-61 and H3 lysine 9 methylation to drive heterochromatin segregation. Using simulations of a minimal polymer system, we show that such interactions are sufficient for the establishment of B compartments and for the phase transition that drives the spatial segregation of heterochromatin from euchromatin. Our findings define genomic, molecular, and mechanistic determinants that are essential for comprehending the role of genome compartmentalization and 3D organization in health and disease.

ORGANISM(S): Caenorhabditis elegans

PROVIDER: GSE271927 | GEO | 2026/06/30

REPOSITORIES: GEO

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