# Unique territorial and compartmental organization of chromosomes in the holocentric silkworm

## TL;DR

The silkworm's genome has a unique 3D structure with a secluded compartment S, which is distinct from typical genome compartments and may involve new mechanisms of chromatin folding.

## Contribution

Discovery of a novel chromatin compartment S in the silkworm genome, which is secluded and exhibits unique loop extrusion and epigenetic features.

## Key findings

- The silkworm genome has a three-compartment structure including a secluded compartment S.
- Compartment S is isolated from other genomic regions and shows high loop extrusion activity.
- S domains are developmentally dynamic and correlate with gene expression changes.

## Abstract

Hallmarks of multicellular eukaryotic genome organization are chromosome territories, compartments, and loop-extrusion-mediated structures, including TADs. However, these have mainly been observed in model organisms, and most eukaryotes remain unexplored. Using Hi-C in the silkworm Bombyx mori we discover a novel chromatin folding structure, compartment S, which is “secluded” from the rest of the chromosome. This compartment exhibits loop extrusion features and a unique genetic and epigenetic landscape, and it localizes towards the periphery of chromosome territories. While euchromatin and heterochromatin display preferential compartmental contacts, S domains are remarkably devoid of contacts with other regions, including with other S domains. In polymer simulations, this contact pattern can only be explained by high loop extrusion activity within compartment S, combined with low extrusion elsewhere throughout the genome. This proposed targeting of loop extrusion is a novel phenomenon, not observed in vertebrate models, but we speculate may extend to more organisms, such as other insects. Overall, our study underscores how evolutionarily conserved mechanisms—compartmentalization and loop extrusion—can be repurposed to create new 3D genome architectures.

Compartmentalization and loop extrusion organize eukaryotic genomes in 3D. Based on Hi-C analyses in Bombyx mori, this work uncovers a new combination of these mechanisms and identifies a novel, secluded compartment “S” that is distinct from the classical A and B and lacks a “checkerboard” pattern.

B. mori chromosomes form strong territories with sparse inter-chromosomal contacts.B. mori genome has a three-compartment organization: A, B and a secluded type dubbed S.Oligopaint-FISH reveals S domains preferentially localize at the periphery of chromosome territories.S domains can appear or disappear during development, coinciding with altered expression of S-located genes.Polymer simulations suggest that B. mori genome organization including the S contact pattern arises from a combination of chromatin-mediated affinities and targeted loop extrusion to S.

B. mori chromosomes form strong territories with sparse inter-chromosomal contacts.

B. mori genome has a three-compartment organization: A, B and a secluded type dubbed S.

Oligopaint-FISH reveals S domains preferentially localize at the periphery of chromosome territories.

S domains can appear or disappear during development, coinciding with altered expression of S-located genes.

Polymer simulations suggest that B. mori genome organization including the S contact pattern arises from a combination of chromatin-mediated affinities and targeted loop extrusion to S.

Hi-C studies show the B. mori genome is organized into A, B and S compartments, with the latter possibly arising from a combination of chromatin-mediated affinities and targeted loop extrusion.