factor for inversion stimulation protein


Summary: A highly abundant DNA binding protein whose expression is strongly correlated with the growth phase of bacteria. The protein plays a role in regulating DNA topology and activation of RIBOSOMAL RNA transcription. It was originally identified as a factor required for inversion stimulation by the Hin recombinase of SALMONELLA and Gin site-specific recombinase of BACTERIOPHAGE MU.

Top Publications

  1. Ussery D, Larsen T, Wilkes K, Friis C, Worning P, Krogh A, et al. Genome organisation and chromatin structure in Escherichia coli. Biochimie. 2001;83:201-12 pubmed
    ..We also show that the regions upstream of genes regulated by H-NS are more curved and have a higher AT content than regions upstream of other genes. These regions in general would also be localised near the replication terminus. ..
  2. Squire D, Xu M, Cole J, Busby S, Browning D. Competition between NarL-dependent activation and Fis-dependent repression controls expression from the Escherichia coli yeaR and ogt promoters. Biochem J. 2009;420:249-57 pubmed publisher
    ..The ogt gene encodes an O6-alkylguanine DNA alkyltransferase and, hence, this is the first report of expression of a DNA repair function being controlled by nitrate ions. ..
  3. Azam T, Hiraga S, Ishihama A. Two types of localization of the DNA-binding proteins within the Escherichia coli nucleoid. Genes Cells. 2000;5:613-26 pubmed
    ..coli could be classified into two groups. One group proteins was distributed uniformly within the nucleoid, but the other group of proteins showed an irregular distribution, forming immuno-stained spots or clumps. ..
  4. Yuan H, Finkel S, Feng J, Kaczor Grzeskowiak M, Johnson R, Dickerson R. The molecular structure of wild-type and a mutant Fis protein: relationship between mutational changes and recombinational enhancer function or DNA binding. Proc Natl Acad Sci U S A. 1991;88:9558-62 pubmed
    ..In contrast, mutations that affect HTH helices C and D, or interactions of these with helix B, have the additional effect of decreasing or eliminating binding to DNA. ..
  5. Aiyar S, McLeod S, Ross W, Hirvonen C, Thomas M, Johnson R, et al. Architecture of Fis-activated transcription complexes at the Escherichia coli rrnB P1 and rrnE P1 promoters. J Mol Biol. 2002;316:501-16 pubmed
    ..Thus, similar Fis-alphaCTD interactions are used for activation of transcription when the activator is bound at very different positions on the DNA. ..
  6. Ball C, Osuna R, Ferguson K, Johnson R. Dramatic changes in Fis levels upon nutrient upshift in Escherichia coli. J Bacteriol. 1992;174:8043-56 pubmed
    ..We suggest that the fluctuations in Fis levels may serve as an early signal of a nutritional upshift and may be important in the physiological roles Fis plays in the cell. ..
  7. Muskhelishvili G, Travers A, Heumann H, Kahmann R. FIS and RNA polymerase holoenzyme form a specific nucleoprotein complex at a stable RNA promoter. EMBO J. 1995;14:1446-52 pubmed
    ..Such a mechanism could overcome transient limitations on the availability of sigma 70 or core polymerase after a prolonged stationary phase. ..
  8. Jackson L, Blake T, Green J. Regulation of ndh expression in Escherichia coli by Fis. Microbiology. 2004;150:407-13 pubmed
  9. Wold S, Crooke E, Skarstad K. The Escherichia coli Fis protein prevents initiation of DNA replication from oriC in vitro. Nucleic Acids Res. 1996;24:3527-32 pubmed
    ..This indicates a negative role for Fis in the regulation of replication initiation. ..

More Information


  1. Nasser W, Schneider R, Travers A, Muskhelishvili G. CRP modulates fis transcription by alternate formation of activating and repressing nucleoprotein complexes. J Biol Chem. 2001;276:17878-86 pubmed
    ..This cross-talk is manifested in alternate formation of functional nucleoprotein complexes exerting either activating or repressing effects on transcription. ..
  2. Schneider R, Travers A, Muskhelishvili G. FIS modulates growth phase-dependent topological transitions of DNA in Escherichia coli. Mol Microbiol. 1997;26:519-30 pubmed
    ..Our results suggest that the primary role of FIS is to modulate chromosomal dynamics during bacterial growth. ..
  3. Shao Y, Feldman Cohen L, Osuna R. Biochemical identification of base and phosphate contacts between Fis and a high-affinity DNA binding site. J Mol Biol. 2008;380:327-39 pubmed publisher
  4. Ninnemann O, Koch C, Kahmann R. The E.coli fis promoter is subject to stringent control and autoregulation. EMBO J. 1992;11:1075-83 pubmed
    ..We show that the fis promoter is subject to stringent control and discuss this unusual feature with respect to the known and putative functions FIS serves in E. coli. ..
  5. Cameron A, Stoebel D, Dorman C. DNA supercoiling is differentially regulated by environmental factors and FIS in Escherichia coli and Salmonella enterica. Mol Microbiol. 2011;80:85-101 pubmed publisher
    ..coli and S. enterica. These findings suggest that E. coli and S. enterica may be unexpectedly divergent in their global regulation of cellular physiology. ..
  6. Falconi M, Brandi A, La Teana A, Gualerzi C, Pon C. Antagonistic involvement of FIS and H-NS proteins in the transcriptional control of hns expression. Mol Microbiol. 1996;19:965-75 pubmed
  7. Gutiérrez Ríos R, Freyre Gonzalez J, Resendis O, Collado Vides J, Saier M, Gosset G. Identification of regulatory network topological units coordinating the genome-wide transcriptional response to glucose in Escherichia coli. BMC Microbiol. 2007;7:53 pubmed
    ..In most cases, each of these modules includes genes encoding physiologically related functions, thus indicating a connection between regulatory network topology and related cellular functions involved in nutrient sensing and metabolism. ..
  8. Hengen P, Bartram S, Stewart L, Schneider T. Information analysis of Fis binding sites. Nucleic Acids Res. 1997;25:4994-5002 pubmed
    ..A sequence in aldB previously reported to be a Fis site, for which information theory predicts no site, did not shift. These results demonstrate that information analysis is useful for predicting Fis DNA binding. ..
  9. Galán B, Manso I, Kolb A, Garcia J, Prieto M. The role of FIS protein in the physiological control of the expression of the Escherichia coli meta-hpa operon. Microbiology. 2008;154:2151-60 pubmed publisher
    ..These results suggest that FIS contributes to silencing the Pg promoter in the exponential phase of growth in an undefined rich medium when FIS is predominantly expressed. ..
  10. Ross W, Thompson J, Newlands J, Gourse R. E.coli Fis protein activates ribosomal RNA transcription in vitro and in vivo. EMBO J. 1990;9:3733-42 pubmed
    ..On the basis of these results, we propose roles for Fis and the upstream activation system in rRNA synthesis. ..
  11. Hirvonen C, Ross W, Wozniak C, Marasco E, Anthony J, Aiyar S, et al. Contributions of UP elements and the transcription factor FIS to expression from the seven rrn P1 promoters in Escherichia coli. J Bacteriol. 2001;183:6305-14 pubmed
    ..These studies have implications for the control of gene expression of unlinked multigene families. ..
  12. Shao Y, Feldman Cohen L, Osuna R. Functional characterization of the Escherichia coli Fis-DNA binding sequence. J Mol Biol. 2008;376:771-85 pubmed publisher
  13. McLeod S, Aiyar S, Gourse R, Johnson R. The C-terminal domains of the RNA polymerase alpha subunits: contact site with Fis and localization during co-activation with CRP at the Escherichia coli proP P2 promoter. J Mol Biol. 2002;316:517-29 pubmed
    ..These experiments define the overall architecture of the proP P2 initiation complex where Fis and CRP each function through a different alphaCTD. ..
  14. Mallik P, Paul B, Rutherford S, Gourse R, Osuna R. DksA is required for growth phase-dependent regulation, growth rate-dependent control, and stringent control of fis expression in Escherichia coli. J Bacteriol. 2006;188:5775-82 pubmed
    ..This work extends our understanding of the multiple factors controlling fis expression and demonstrates the generality of the DksA requirement for regulation of kinetically similar promoters. ..
  15. Kelly A, Goldberg M, Carroll R, Danino V, Hinton J, Dorman C. A global role for Fis in the transcriptional control of metabolism and type III secretion in Salmonella enterica serovar Typhimurium. Microbiology. 2004;150:2037-53 pubmed
    ..The data reported reveal the central role played by Fis in coordinating the expression of both housekeeping and virulence factors required by S. typhimurium during life in the gut lumen or during systemic infection of host cells. ..
  16. Grainger D, Goldberg M, Lee D, Busby S. Selective repression by Fis and H-NS at the Escherichia coli dps promoter. Mol Microbiol. 2008;68:1366-77 pubmed publisher
    ..Our data suggest a simple model to explain how the Dps-dependent super-compaction of the folded chromosome is triggered as cell growth ceases. ..
  17. Browning D, Cole J, Busby S. Regulation by nucleoid-associated proteins at the Escherichia coli nir operon promoter. J Bacteriol. 2008;190:7258-67 pubmed publisher
    ..Differences in the upstream IHF and Fis binding sites at the nir promoter in related enteric bacteria fix the level of nir operon expression under anaerobic growth conditions. ..
  18. Weinstein Fischer D, Elgrably Weiss M, Altuvia S. Escherichia coli response to hydrogen peroxide: a role for DNA supercoiling, topoisomerase I and Fis. Mol Microbiol. 2000;35:1413-20 pubmed
    ..We also show that a fis deficient mutant strain is extremely sensitive to hydrogen peroxide. Our results suggest that topA activation by Fis is an important component of the Escherichia coli response to oxidative stress. ..
  19. Safo M, Yang W, Corselli L, Cramton S, Yuan H, Johnson R. The transactivation region of the fis protein that controls site-specific DNA inversion contains extended mobile beta-hairpin arms. EMBO J. 1997;16:6860-73 pubmed
    ..The emerging picture for this regulatory motif is that contacts with the recombinase at the tip of the mobile beta-arms activate the DNA invertase in the context of an invertasome complex. ..
  20. Gonzalez Gil G, Kahmann R, Muskhelishvili G. Regulation of crp transcription by oscillation between distinct nucleoprotein complexes. EMBO J. 1998;17:2877-85 pubmed
    ..Our results suggest that the control of crp transcription is achieved by oscillation in the composition of these regulatory nucleoprotein complexes in response to the physiological state of the cell. ..
  21. Blot N, Mavathur R, Geertz M, Travers A, Muskhelishvili G. Homeostatic regulation of supercoiling sensitivity coordinates transcription of the bacterial genome. EMBO Rep. 2006;7:710-5 pubmed
    ..We infer that a homeostatic mechanism organizing the supercoiling sensitivity is coordinating the growth-phase-dependent transcription of the genome. ..
  22. Browning D, Grainger D, Busby S. Effects of nucleoid-associated proteins on bacterial chromosome structure and gene expression. Curr Opin Microbiol. 2010;13:773-80 pubmed publisher
    ..Some specific examples, involving the E. coli IHF and Fis proteins, that illustrate new principles, are described in detail. ..
  23. Cho B, Knight E, Barrett C, Palsson B. Genome-wide analysis of Fis binding in Escherichia coli indicates a causative role for A-/AT-tracts. Genome Res. 2008;18:900-10 pubmed publisher
    ..These novel results provide new insight into how Fis modulates DNA topology at a genome scale and thus advance our understanding of the architectural bases of the E. coli nucleoid. ..
  24. Lenz D, Bassler B. The small nucleoid protein Fis is involved in Vibrio cholerae quorum sensing. Mol Microbiol. 2007;63:859-71 pubmed
  25. Skoko D, Yoo D, Bai H, Schnurr B, Yan J, McLeod S, et al. Mechanism of chromosome compaction and looping by the Escherichia coli nucleoid protein Fis. J Mol Biol. 2006;364:777-98 pubmed
    ..These results suggest that Fis may play a role in vivo as a domain barrier element by organizing DNA loops within the E. coli chromosome. ..
  26. Browning D, Grainger D, Beatty C, Wolfe A, Cole J, Busby S. Integration of three signals at the Escherichia coli nrf promoter: a role for Fis protein in catabolite repression. Mol Microbiol. 2005;57:496-510 pubmed
    ..Hence, Fis protein is a major factor responsible for catabolite repression at the nrf promoter, and Fis can override activation by FNR and NarL or NarP. ..
  27. Mallik P, Pratt T, Beach M, Bradley M, Undamatla J, Osuna R. Growth phase-dependent regulation and stringent control of fis are conserved processes in enteric bacteria and involve a single promoter (fis P) in Escherichia coli. J Bacteriol. 2004;186:122-35 pubmed
    ..We further show how certain conditions used in the primer extension reactions can generate artifacts resulting from secondary annealing events that are the likely source of incorrect assignment of additional fis promoters. ..
  28. Schneider R, Travers A, Kutateladze T, Muskhelishvili G. A DNA architectural protein couples cellular physiology and DNA topology in Escherichia coli. Mol Microbiol. 1999;34:953-64 pubmed
    ..We propose that FIS is involved in coupling cellular physiology to the topology of the bacterial chromosome. ..
  29. Hengen P, Lyakhov I, Stewart L, Schneider T. Molecular flip-flops formed by overlapping Fis sites. Nucleic Acids Res. 2003;31:6663-73 pubmed
    ..Alternatively, the flip-flop could represent part of an on-off switch for replication. Because they can be used to create precise switched states, molecular flip-flops could be used as the basis of a novel molecular computer. ..
  30. Beach M, Osuna R. Identification and characterization of the fis operon in enteric bacteria. J Bacteriol. 1998;180:5932-46 pubmed
    ..However, their promoter strengths vary, as do their responses to Fis autoregulation and integration host factor stimulation. ..
  31. Perkins Balding D, Dias D, Glasgow A. Location, degree, and direction of DNA bending associated with the Hin recombinational enhancer sequence and Fis-enhancer complex. J Bacteriol. 1997;179:4747-53 pubmed
    ..The positions and directions of DNA bends associated with the Fis-recombinational complex support a direct role for Fis-induced DNA bending in assembly of the active invertasome. ..
  32. Finkel S, Johnson R. The Fis protein: it's not just for DNA inversion anymore. Mol Microbiol. 1992;6:3257-65 pubmed
    ..The X-ray crystal structure of Fis has been determined and insights into its mode of DNA binding and mechanisms of action in these disparate systems are being made. ..
  33. Blaby I, Summers D. The role of FIS in the Rcd checkpoint and stable maintenance of plasmid ColE1. Microbiology. 2009;155:2676-82 pubmed publisher
    ..Rcd transcription is triggered in plasmid dimers by the lifting of XerCD-mediated repression in the synaptic complex. ..
  34. Slany R, Kersten H. The promoter of the tgt/sec operon in Escherichia coli is preceded by an upstream activation sequence that contains a high affinity FIS binding site. Nucleic Acids Res. 1992;20:4193-8 pubmed
    ..An approximately two-fold activation of the promoter by the UAS element was observed. ..
  35. Kostrewa D, Granzin J, Koch C, Choe H, Raghunathan S, Wolf W, et al. Three-dimensional structure of the E. coli DNA-binding protein FIS. Nature. 1991;349:178-80 pubmed
    ..We infer from model building that DNA has to bend for tight binding to FIS. ..
  36. Koch C, Vandekerckhove J, Kahmann R. Escherichia coli host factor for site-specific DNA inversion: cloning and characterization of the fis gene. Proc Natl Acad Sci U S A. 1988;85:4237-41 pubmed
    ..Fis is nonessential for Es. coli growth; however, inversion of the G segment of a Mu prophage was not detected in the fis mutant. The fis gene is located between 71 and 72 min on the Es. coli genetic map. ..
  37. Bokal A, Ross W, Gourse R. The transcriptional activator protein FIS: DNA interactions and cooperative interactions with RNA polymerase at the Escherichia coli rrnB P1 promoter. J Mol Biol. 1995;245:197-207 pubmed
  38. Nasser W, Rochman M, Muskhelishvili G. Transcriptional regulation of fis operon involves a module of multiple coupled promoters. EMBO J. 2002;21:715-24 pubmed
    ..We infer that these coupled promoters represent a regulatory module and propose a novel "dynamic balance" mechanism involved in the transcriptional control of the fis operon. ..
  39. Ohniwa R, Morikawa K, Kim J, Ohta T, Ishihama A, Wada C, et al. Dynamic state of DNA topology is essential for genome condensation in bacteria. EMBO J. 2006;25:5591-602 pubmed
    ..These results indicate that the topology of DNA is dynamically transmutable and that the topology control is important for Dps-induced nucleoid condensation. ..
  40. Pemberton I, Muskhelishvili G, Travers A, Buckle M. FIS modulates the kinetics of successive interactions of RNA polymerase with the core and upstream regions of the tyrT promoter. J Mol Biol. 2002;318:651-63 pubmed
    ..We further suggest that FIS plays a similar role and may facilitate polymerase escape. ..
  41. Merickel S, Sanders E, Vazquez Ibar J, Johnson R. Subunit exchange and the role of dimer flexibility in DNA binding by the Fis protein. Biochemistry. 2002;41:5788-98 pubmed
    ..These results support a model in which the unusually short distance between DNA recognition helices on Fis is accommodated primarily through bending of the DNA. ..
  42. Browning D, Cole J, Busby S. Suppression of FNR-dependent transcription activation at the Escherichia coli nir promoter by Fis, IHF and H-NS: modulation of transcription initiation by a complex nucleo-protein assembly. Mol Microbiol. 2000;37:1258-69 pubmed
    ..NarL and NarP can relieve both IHF- and Fis-mediated repression, but are unable to counteract H-NS-mediated repression. ..
  43. Skoko D, Yan J, Johnson R, Marko J. Low-force DNA condensation and discontinuous high-force decondensation reveal a loop-stabilizing function of the protein Fis. Phys Rev Lett. 2005;95:208101 pubmed
    ..Our experiments suggest that Fis may play a role in vivo stabilizing the "loop-domain" structure of the bacterial chromosome. ..
  44. Lazarus L, Travers A. The Escherichia coli FIS protein is not required for the activation of tyrT transcription on entry into exponential growth. EMBO J. 1993;12:2483-94 pubmed
    ..In principle such a mechanism could confer a significant selective advantage thus accounting for the conservation of FIS binding sites in the regulatory regions of stable RNA promoters. ..
  45. Hardy C, Cozzarelli N. A genetic selection for supercoiling mutants of Escherichia coli reveals proteins implicated in chromosome structure. Mol Microbiol. 2005;57:1636-52 pubmed
    ..We suggest that at least H-NS, Fis and perhaps TktA assist directly in the supercoiling of domains by forming topological barriers on the E. coli chromosome. ..
  46. Dorman C. H-NS: a universal regulator for a dynamic genome. Nat Rev Microbiol. 2004;2:391-400 pubmed
  47. Schechter L, Jain S, Akbar S, Lee C. The small nucleoid-binding proteins H-NS, HU, and Fis affect hilA expression in Salmonella enterica serovar Typhimurium. Infect Immun. 2003;71:5432-5 pubmed
    ..Modulation of hilA by counteracting repressing and derepressing mechanisms may allow Salmonella serovar Typhimurium to regulate its virulence genes in response to different situations in vivo. ..
  48. Travers A, Muskhelishvili G. DNA microloops and microdomains: a general mechanism for transcription activation by torsional transmission. J Mol Biol. 1998;279:1027-43 pubmed
    ..In this process, which we term torsional transmission, a major function of the activator is to act as a local topological homeostat. We argue that the same mechanism may also be employed in site-specific DNA inversion. ..
  49. Shultzaberger R, Roberts L, Lyakhov I, Sidorov I, Stephen A, Fisher R, et al. Correlation between binding rate constants and individual information of E. coli Fis binding sites. Nucleic Acids Res. 2007;35:5275-83 pubmed
    ..Finally, we observed a break in the binding curve around zero bits of information. The break is expected from information theory because it represents the coding demarcation between specific and nonspecific binding. ..
  50. Green J, Anjum M, Guest J. The ndh-binding protein (Nbp) regulates the ndh gene of Escherichia coli in response to growth phase and is identical to Fis. Mol Microbiol. 1996;20:1043-55 pubmed
  51. Martin R, Rosner J. Fis, an accessorial factor for transcriptional activation of the mar (multiple antibiotic resistance) promoter of Escherichia coli in the presence of the activator MarA, SoxS, or Rob. J Bacteriol. 1997;179:7410-9 pubmed
    ..Thus, Fis acts as an accessory transcriptional activator at the mar promoter. ..
  52. Dorman C, Deighan P. Regulation of gene expression by histone-like proteins in bacteria. Curr Opin Genet Dev. 2003;13:179-84 pubmed
    ..Recent advances have also been assisted by insights into the effects the histone-like proteins exert on DNA structure not only at specific promoters but throughout the genome. ..
  53. Kahramanoglou C, Seshasayee A, Prieto A, Ibberson D, Schmidt S, Zimmermann J, et al. Direct and indirect effects of H-NS and Fis on global gene expression control in Escherichia coli. Nucleic Acids Res. 2011;39:2073-91 pubmed publisher
    ..Our study serves as a proof-of-principle for the use of ChIP-seq for global DNA-binding proteins in bacteria, which should become significantly more economical and feasible with the development of multiplexing techniques. ..