A Well-Mixed E. coli Genome: Widespread Contacts Revealed by Tracking Mu Transposition

Cell. 2020 Feb 20;180(4):703-716.e18. doi: 10.1016/j.cell.2020.01.031. Epub 2020 Feb 13.

Abstract

The three-dimensional structures of chromosomes are increasingly being recognized as playing a major role in cellular regulatory states. The efficiency and promiscuity of phage Mu transposition was exploited to directly measure in vivo interactions between genomic loci in E. coli. Two global organizing principles have emerged: first, the chromosome is well-mixed and uncompartmentalized, with transpositions occurring freely between all measured loci; second, several gene families/regions show "clustering": strong three-dimensional co-localization regardless of linear genomic distance. The activities of the SMC/condensin protein MukB and nucleoid-compacting protein subunit HU-α are essential for the well-mixed state; HU-α is also needed for clustering of 6/7 ribosomal RNA-encoding loci. The data are explained by a model in which the chromosomal structure is driven by dynamic competition between DNA replication and chromosomal relaxation, providing a foundation for determining how region-specific properties contribute to both chromosomal structure and gene regulation.

Keywords: Bacteriophage Mu; E. coli; HU; MukBEF; NAP; SMC; chromosome conformation capture; chromosome organization; macrodomains; transposition.

Publication types

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

MeSH terms

  • Bacteriophage mu / genetics*
  • Chromosomal Proteins, Non-Histone / genetics
  • Chromosomal Proteins, Non-Histone / metabolism
  • Chromosomes, Bacterial / chemistry
  • Chromosomes, Bacterial / genetics*
  • DNA Transposable Elements*
  • DNA, Bacterial / chemistry
  • DNA, Bacterial / genetics
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism
  • Escherichia coli
  • Escherichia coli Proteins / genetics
  • Escherichia coli Proteins / metabolism
  • Genome, Bacterial
  • Nucleic Acid Conformation
  • Transposases / genetics
  • Transposases / metabolism

Substances

  • Chromosomal Proteins, Non-Histone
  • DNA Transposable Elements
  • DNA, Bacterial
  • DNA-Binding Proteins
  • Escherichia coli Proteins
  • MukB protein, E coli
  • hupA protein, E coli
  • mu transposase
  • Transposases