Sub-kb Hi-C in D. melanogaster reveals conserved characteristics of TADs between insect and mammalian cells

Nat Commun. 2018 Jan 15;9(1):188. doi: 10.1038/s41467-017-02526-9.

Abstract

Topologically associating domains (TADs) are fundamental elements of the eukaryotic genomic structure. However, recent studies suggest that the insulating complexes, CTCF/cohesin, present at TAD borders in mammals are absent from those in Drosophila melanogaster, raising the possibility that border elements are not conserved among metazoans. Using in situ Hi-C with sub-kb resolution, here we show that the D. melanogaster genome is almost completely partitioned into >4000 TADs, nearly sevenfold more than previously identified. The overwhelming majority of these TADs are demarcated by the insulator complexes, BEAF-32/CP190, or BEAF-32/Chromator, indicating that these proteins may play an analogous role in flies as that of CTCF/cohesin in mammals. Moreover, extended regions previously thought to be unstructured are shown to consist of small contiguous TADs, a property also observed in mammals upon re-examination. Altogether, our work demonstrates that fundamental features associated with the higher-order folding of the genome are conserved from insects to mammals.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biological Evolution
  • CCCTC-Binding Factor / genetics
  • CCCTC-Binding Factor / metabolism
  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / metabolism
  • Chromatin / chemistry
  • Chromatin / ultrastructure*
  • Chromatin Assembly and Disassembly
  • Chromosomal Proteins, Non-Histone / genetics
  • Chromosomal Proteins, Non-Histone / metabolism
  • Chromosome Mapping / instrumentation
  • Chromosome Mapping / methods*
  • Chromosomes, Insect / chemistry
  • Chromosomes, Insect / ultrastructure*
  • Cohesins
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism
  • Drosophila Proteins / genetics
  • Drosophila Proteins / metabolism
  • Drosophila melanogaster / genetics*
  • Drosophila melanogaster / ultrastructure
  • Eye Proteins / genetics
  • Eye Proteins / metabolism
  • Gene Expression
  • Genome, Insect*
  • Humans
  • Mammals / genetics*
  • Microtubule-Associated Proteins / genetics
  • Microtubule-Associated Proteins / metabolism
  • Molecular Conformation
  • Nuclear Matrix-Associated Proteins / genetics
  • Nuclear Matrix-Associated Proteins / metabolism
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism

Substances

  • BEAF-32 protein, Drosophila
  • CCCTC-Binding Factor
  • CP190 protein, Drosophila
  • CTCF protein, human
  • Cell Cycle Proteins
  • Chro protein, Drosophila
  • Chromatin
  • Chromosomal Proteins, Non-Histone
  • DNA-Binding Proteins
  • Drosophila Proteins
  • Eye Proteins
  • Microtubule-Associated Proteins
  • Nuclear Matrix-Associated Proteins
  • Nuclear Proteins