Research Article: Hopping into a hot seat: Role of DNA structural features on IS5-mediated gene activation and inactivation under stress

Date Published: June 30, 2017

Publisher: Public Library of Science

Author(s): M. Zafri Humayun, Zhongge Zhang, Anna M. Butcher, Aref Moshayedi, Milton H. Saier, Ruslan Kalendar.


Insertion sequence elements (IS elements) are proposed to play major roles in shaping the genetic and phenotypic landscapes of prokaryotic cells. Recent evidence has raised the possibility that environmental stress conditions increase IS hopping into new sites, and often such hopping has the phenotypic effect of relieving the stress. Although stress-induced targeted mutations have been reported for a number of E. coli genes, the glpFK (glycerol utilization) and the cryptic bglGFB (β-glucoside utilization) systems are among the best characterized where the effects of IS insertion-mediated gene activation are well-characterized at the molecular level. In the glpFK system, starvation of cells incapable of utilizing glycerol leads to an IS5 insertion event that activates the glpFK operon, and enables glycerol utilization. In the case of the cryptic bglGFB operon, insertion of IS5 (and other IS elements) into a specific region in the bglG upstream sequence has the effect of activating the operon in both growing cells, and in starving cells. However, a major unanswered question in the glpFK system, the bgl system, as well as other examples, has been why the insertion events are promoted at specific locations, and how the specific stress condition (glycerol starvation for example) can be mechanistically linked to enhanced insertion at a specific locus. In this paper, we show that a specific DNA structural feature (superhelical stress-induced duplex destabilization, SIDD) is associated with “stress-induced” IS5 insertion in the glpFK, bglGFB, flhDC, fucAO and nfsB systems. We propose a speculative mechanistic model that links specific environmental conditions to the unmasking of an insertional hotspot in the glpFK system. We demonstrate that experimentally altering the predicted stability of a SIDD element in the nfsB gene significantly impacts IS5 insertion at its hotspot.

Partial Text

Transposable genetic elements, once considered to be exotic “DNA level parasites” that enabled non-Mendelian transmission of genetic traits, are now recognized to be members of a large collection of genetic elements collectively termed the”mobilome” that constitute important but variable parts of most examined genomes [1]. In this view, the genomes consist of a fixed “core genome” and a collection of variable genetic elements that include plasmids, viruses, transposons, insertion sequences, integrative conjugative elements (ICE), as well as a large number of related sequences that are not always easily recognized. The mobilome, important for all organisms, has played an especially critical role in shaping the prokaryotic world. A testament to the significance of the mobilome is the conclusion that transposases, the genes that confer mobility to transposable elements, are the most ubiquitous genes in nature [2].




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