Silencing of toxic gene expression by Fis

Abstract

Bacteria and bacteriophages have evolved DNA modification as a strategy to protect their genomes. Mom protein of bacteriophage Mu modifies the phage DNA, rendering it refractile to numerous restriction enzymes and in turn enabling the phage to successfully invade a variety of hosts. A strong fortification, a combined activity of the phage and host factors, prevents untimely expression of mom and associated toxic effects. Here, we identify the bacterial chromatin architectural protein Fis as an additional player in this crowded regulatory cascade. Both in vivo and in vitro studies described here indicate that Fis acts as a transcriptional repressor of mom promoter. Further, our data shows that Fis mediates its repressive effect by denying access to RNA polymerase at mom promoter. We propose that a combined repressive effect of Fis and previously characterized negative regulatory factors could be responsible to keep the gene silenced most of the time. We thus present a new facet of Fis function in Mu biology. In addition to bringing about overall downregulation of Mu genome, it also ensures silencing of the advantageous but potentially lethal mom gene.

Transposable Prophage Mu Is Organized as a Stable Chromosomal Domain of E. coli

“…Deletion of the HU-binding site at the Mu L end had a small effect, while deletion of the Fis-binding enhancer site sis (Δ sis ) had no effect. Recent experiments have identified a set of three Fis-binding sites within the promoter region of the mom gene near the R end [39] . A deletion spanning all three sites (ΔP mom ) also had no effect.…”

Temporal control of Dickeya dadantii main virulence gene expression by growth phase-dependent alteration of regulatory nucleoprotein complexes

“…Importantly, FIS2 also overlaps the CRP2 binding site. These four putative sites were inactivated separately, or in various combinations, by substituting the conserved G at the position 1 and the conserved C at the position 15 by Ts [36], as described in Fig 1.…”

“…Similar regulatory mechanisms can be found not only at different promoters in single species but also in different species, whereby involvement of several FIS binding sites in promoter repression is not unusual. A well-known example is the negative autoregulation of the fis promoter involving numerous FIS binding sites [50], and there are other examples, such as the mom [36] and the gyr promoters of E. coli [6] and Salmonella [51], to name just a few.…”

Emergence of a novel immune-evasion strategy from an ancestral protein fold in bacteriophage Mu

“…DNA modification by Mom enables dramatically higher (up to 10 4 fold) efficiencies of plating compared to Mu momphages on restricting strains of E. coli 4 . Owing to the selective advantage, numerous host and phage-encoded proteins have evolved to regulate the potentially lethal mom gene in diverse ways 4,10,11 . While intricate details surrounding mom gene regulation have been teased apart, the biochemistry of Mom and molecular mechanisms underlying the modification are still shrouded in mystery.…”