Lamina-Dependent Stretching and Unconventional Chromosome Compartments in Early C. elegans Embryos

Mol Cell. 2020 Apr 2;78(1):96-111.e6. doi: 10.1016/j.molcel.2020.02.006. Epub 2020 Feb 26.

Abstract

Current models suggest that chromosome domains segregate into either an active (A) or inactive (B) compartment. B-compartment chromatin is physically separated from the A compartment and compacted by the nuclear lamina. To examine these models in the developmental context of C. elegans embryogenesis, we undertook chromosome tracing to map the trajectories of entire autosomes. Early embryonic chromosomes organized into an unconventional barbell-like configuration, with two densely folded B compartments separated by a central A compartment. Upon gastrulation, this conformation matured into conventional A/B compartments. We used unsupervised clustering to uncover subpopulations with differing folding properties and variable positioning of compartment boundaries. These conformations relied on tethering to the lamina to stretch the chromosome; detachment from the lamina compacted, and allowed intermingling between, A/B compartments. These findings reveal the diverse conformations of early embryonic chromosomes and uncover a previously unappreciated role for the lamina in systemic chromosome stretching.

Keywords: 3D genome; chromosome conformation; development; early embryogenesis; multiplexed DNA FISH; nuclear lamina; unsupervised clustering.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Caenorhabditis elegans / embryology
  • Caenorhabditis elegans / genetics*
  • Chromosomes / chemistry*
  • Chromosomes / ultrastructure
  • Embryo, Nonmammalian / ultrastructure
  • Gastrulation / genetics
  • In Situ Hybridization, Fluorescence
  • Molecular Conformation
  • Nuclear Lamina / physiology*