integration host factors


Summary: Bacterial proteins that are used by BACTERIOPHAGES to incorporate their DNA into the DNA of the "host" bacteria. They are DNA-binding proteins that function in genetic recombination as well as in transcriptional and translational regulation.

Top Publications

  1. Wang H, Chong S. Visualization of coupled protein folding and binding in bacteria and purification of the heterodimeric complex. Proc Natl Acad Sci U S A. 2003;100:478-83 pubmed
    ..Such interaction has been previously shown to occur between the E. coli integration host factors alpha and beta, and between the domains of the general transcriptional coactivator cAMP response element ..
  2. Hwang D, Kornberg A. Opposed actions of regulatory proteins, DnaA and IciA, in opening the replication origin of Escherichia coli. J Biol Chem. 1992;267:23087-91 pubmed
    ..The selective interactions of DnaA and IciA proteins with the 13-mer region appear to be components of the on/off switch that controls initiation of E. coli chromosomal replication. ..
  3. Calb R, Davidovitch A, Koby S, Giladi H, Goldenberg D, Margalit H, et al. Structure and function of the Pseudomonas putida integration host factor. J Bacteriol. 1996;178:6319-26 pubmed
    ..It was further shown that the ihfA P. putida mutant strain carrying the TOL plasmid was defective in the degradation of the aromatic model compound benzyl alcohol, proving the unique role of IHF in xyl operon promoter regulation...
  4. Brassinga A, Siam R, McSween W, Winkler H, Wood D, Marczynski G. Conserved response regulator CtrA and IHF binding sites in the alpha-proteobacteria Caulobacter crescentus and Rickettsia prowazekii chromosomal replication origins. J Bacteriol. 2002;184:5789-99 pubmed
    ..Therefore, CtrA and IHF regulatory proteins have similar binding patterns in both replication origins, and we propose that CzcR is a global cell cycle regulator in R. prowazekii...
  5. Grainger D, Hurd D, Goldberg M, Busby S. Association of nucleoid proteins with coding and non-coding segments of the Escherichia coli genome. Nucleic Acids Res. 2006;34:4642-52 pubmed
    ..Hence some targets are associated with combinations of bound FIS, H-NS and IHF. In addition, many regions associated with FIS and H-NS are also associated with RNA polymerase. ..
  6. Sarkar T, Petrov A, Vitko J, Santai C, Harvey S, Mukerji I, et al. Integration host factor (IHF) dictates the structure of polyamine-DNA condensates: implications for the role of IHF in the compaction of bacterial chromatin. Biochemistry. 2009;48:667-75 pubmed publisher
    ..We propose that a common function of IHF and HU in bacterial cells is to facilitate DNA organization in the nucleoid by the introduction of sharp bends in chromosomal DNA. ..
  7. Mangan M, Lucchini S, Danino V, Cróinín T, Hinton J, Dorman C. The integration host factor (IHF) integrates stationary-phase and virulence gene expression in Salmonella enterica serovar Typhimurium. Mol Microbiol. 2006;59:1831-47 pubmed
    ..Although the three mutants showed considerable overlaps in the genes affected by the ihf lesions, the observed patterns were not identical, showing that S. Typhimurium has not one but three overlapping IHF regulons. ..
  8. Sugimura S, Crothers D. Stepwise binding and bending of DNA by Escherichia coli integration host factor. Proc Natl Acad Sci U S A. 2006;103:18510-4 pubmed
    ..Our observations on the bending step kinetics are in agreement with results using the temperature-jump kinetic method. ..
  9. Sze C, Laurie A, Shingler V. In vivo and in vitro effects of integration host factor at the DmpR-regulated sigma(54)-dependent Po promoter. J Bacteriol. 2001;183:2842-51 pubmed
    ..Mechanistic implications are discussed in the context of a model in which IHF binding results in transduction of DNA instability from an A+T-rich region to the melt region of the promoter. ..

More Information


  1. Goodman S, Velten N, Gao Q, Robinson S, Segall A. In vitro selection of integration host factor binding sites. J Bacteriol. 1999;181:3246-55 pubmed
    ..Despite finding individual sequences that varied over 100-fold in affinity for IHF, we found no apparent correlation between affinity and function. ..
  2. Zulianello L, de la Gorgue de Rosny E, van Ulsen P, van de Putte P, Goosen N. The HimA and HimD subunits of integration host factor can specifically bind to DNA as homodimers. EMBO J. 1994;13:1534-40 pubmed
    ..A comparable fusion protein with only the DNA-binding domains of HimD forms less stable complexes, suggesting that sequence-specific contacts between IHF and the ihf consensus are mainly provided by the HimA subunit. ..
  3. Lin J, Chen H, Droge P, Yan J. Physical organization of DNA by multiple non-specific DNA-binding modes of integration host factor (IHF). PLoS ONE. 2012;7:e49885 pubmed publisher
    ..Our findings provide important insights into how IHF contributes to bacterial chromatin organization, gene regulation, and biofilm formation. ..
  4. Senear D, Tretyachenko Ladokhina V, Opel M, Aeling K, Hatfield G, Franklin L, et al. Pressure dissociation of integration host factor-DNA complexes reveals flexibility-dependent structural variation at the protein-DNA interface. Nucleic Acids Res. 2007;35:1761-72 pubmed
    ..Biol. 310, 379-401, 2001). We propose that the volume changes reflect differences in hydration that arise from structural variation at IHF-DNA interfaces while the resulting energetic compensation maintains the same net binding energy. ..
  5. 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. ..
  6. Lynch T, Read E, Mattis A, Gardner J, Rice P. Integration host factor: putting a twist on protein-DNA recognition. J Mol Biol. 2003;330:493-502 pubmed
    ..Comparison of these structures reveals that DNA twist plays a major role in DNA recognition by IHF, and that this geometric parameter is dependent on the dinucleotide step and not on the bound IHF variant. ..
  7. Sieira R, Comerci D, Pietrasanta L, Ugalde R. Integration host factor is involved in transcriptional regulation of the Brucella abortus virB operon. Mol Microbiol. 2004;54:808-22 pubmed
    ..These data indicate that IHF plays a key role during intracellular virB operon expression being required for the biogenesis of the endoplasmic reticulum-derived replicative vacuole. ..
  8. Colland F, Barth M, Hengge Aronis R, Kolb A. sigma factor selectivity of Escherichia coli RNA polymerase: role for CRP, IHF and lrp transcription factors. EMBO J. 2000;19:3028-37 pubmed
    ..This different ability of the two holoenzymes to interact productively with promoters once assembled in complex nucleoprotein structures may be a crucial factor in generating sigma(S) selectivity in vivo. ..
  9. Swinger K, Rice P. IHF and HU: flexible architects of bent DNA. Curr Opin Struct Biol. 2004;14:28-35 pubmed
    ..These techniques include time-resolved synchrotron X-ray footprinting, differential scanning calorimetry, isothermal titration calorimetry and single-molecule experiments. ..
  10. Buisine N, Tang C, Chalmers R. Transposon-like Correia elements: structure, distribution and genetic exchange between pathogenic Neisseria sp. FEBS Lett. 2002;522:52-8 pubmed
    ..Phylogenetic analysis suggests that their presence predates the divergence of Neisseria meningitidis and Neisseria gonorrhoeae. ..
  11. Jovanovic G, Model P. PspF and IHF bind co-operatively in the psp promoter-regulatory region of Escherichia coli. Mol Microbiol. 1997;25:473-81 pubmed
    ..In the absence of IHF, in vivo autoregulation of pspF transcription is lifted and, consequently, PspF production is increased, indicating that IHF enhances PspF binding to the psp enhancer in vivo. ..
  12. Ellenberger T, Landy A. A good turn for DNA: the structure of integration host factor bound to DNA. Structure. 1997;5:153-7 pubmed
    ..IHF exerts leverage in the minor groove and wraps DNA around the body of the protein, providing another example of sequence-specific recognition of the minor groove. ..
  13. Freundlich M, Ramani N, Mathew E, Sirko A, Tsui P. The role of integration host factor in gene expression in Escherichia coli. Mol Microbiol. 1992;6:2557-63 pubmed
  14. 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. ..
  15. Santero E, Hoover T, North A, Berger D, Porter S, Kustu S. Role of integration host factor in stimulating transcription from the sigma 54-dependent nifH promoter. J Mol Biol. 1992;227:602-20 pubmed
  16. Goosen N, van de Putte P. The regulation of transcription initiation by integration host factor. Mol Microbiol. 1995;16:1-7 pubmed
    ..In addition, it summarizes the evidence indicating that IHF can stimulate transcription via a direct interaction with RNA polymerase and explores the possibility that the asymmetry of the IHF protein might reflect such an interaction. ..
  17. Yang Y, Song E, Willemse J, Park S, Kim W, Kim E, et al. A novel function of Streptomyces integration host factor (sIHF) in the control of antibiotic production and sporulation in Streptomyces coelicolor. Antonie Van Leeuwenhoek. 2012;101:479-92 pubmed publisher
    Bacterial integration host factors (IHFs) play important roles in site-specific recombination, DNA replication, transcription, genome organization and bacterial pathogenesis...
  18. Hwang D, Kornberg A. Opening of the replication origin of Escherichia coli by DnaA protein with protein HU or IHF. J Biol Chem. 1992;267:23083-6 pubmed
    ..The footprint of the nucleotide-free form of the protein, by contrast, was more extensive and thus, less specific. ..
  19. Sewitz S, Crellin P, Chalmers R. The positive and negative regulation of Tn10 transposition by IHF is mediated by structurally asymmetric transposon arms. Nucleic Acids Res. 2003;31:5868-76 pubmed
    ..This suggests that inhibition of target interactions is due to steric hindrance of the target binding site by a single IHF-folded transposon arm. ..
  20. Crellin P, Sewitz S, Chalmers R. DNA looping and catalysis; the IHF-folded arm of Tn10 promotes conformational changes and hairpin resolution. Mol Cell. 2004;13:537-47 pubmed
    ..Further evidence suggests that the molecular mechanism responsible may be mechanical stress in the IHF loop, related to a change in the relative position of the transposase contacts that anchor the loop on either side. ..
  21. Goodrich J, Schwartz M, McClure W. Searching for and predicting the activity of sites for DNA binding proteins: compilation and analysis of the binding sites for Escherichia coli integration host factor (IHF). Nucleic Acids Res. 1990;18:4993-5000 pubmed
    ..The MacTargsearch program and its potential usefulness in searching for other sites and predicting their relative activities is discussed. ..
  22. Liebler E, Diederichsen U. From IHF protein to design and synthesis of a sequence-specific DNA bending peptide. Org Lett. 2004;6:2893-6 pubmed
    ..The latter was designed for specific DNA recognition in the minor groove followed by bending of the double strand. ..
  23. Paul L, Blumenthal R, Matthews R. Activation from a distance: roles of Lrp and integration host factor in transcriptional activation of gltBDF. J Bacteriol. 2001;183:3910-8 pubmed
    ..Based on these results, we suggest that IHF plays a crucial architectural role, bringing the distant Lrp complex in close proximity to the promoter-bound RNA polymerase. ..
  24. 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. ..
  25. Goodman S, Obergfell K, Jurcisek J, Novotny L, Downey J, Ayala E, et al. Biofilms can be dispersed by focusing the immune system on a common family of bacterial nucleoid-associated proteins. Mucosal Immunol. 2011;4:625-37 pubmed publisher
    ..We discuss the prospects for targeting DNABII family members as a potential universal strategy for treating biofilm diseases...
  26. Parekh B, Sheridan S, Hatfield G. Effects of integration host factor and DNA supercoiling on transcription from the ilvPG promoter of Escherichia coli. J Biol Chem. 1996;271:20258-64 pubmed
    ..Therefore, IHF binding does not activate transcription simply by increasing the local negative supercoiling of the DNA helix in the downstream promoter region or by differential binding to relaxed and supercoiled DNA templates. ..
  27. Sun D, Hurley L, Harshey R. Structural distortions induced by integration host factor (IHF) at the H' site of phage lambda probed by (+)-CC-1065, pluramycin, and KMnO4 and by DNA cyclization studies. Biochemistry. 1996;35:10815-27 pubmed
    ..These studies suggest that IHF-induced DNA bending is accompanied by the introduction of a DNA node, DNA unwinding, and/or by some other DNA distortion. An enhanced binding and stability of IHF was observed on small circular DNA. ..
  28. Rice P, Yang S, Mizuuchi K, Nash H. Crystal structure of an IHF-DNA complex: a protein-induced DNA U-turn. Cell. 1996;87:1295-306 pubmed
    ..One such readout involves a six-base A tract, providing evidence for the importance of a narrow minor groove. ..
  29. Wang W, Li G, Chen C, Xie X, Zhuang X. Chromosome organization by a nucleoid-associated protein in live bacteria. Science. 2011;333:1445-9 pubmed publisher
    ..Deleting H-NS led to substantial chromosome reorganization. These observations demonstrate that H-NS plays a key role in global chromosome organization in bacteria. ..
  30. Leoni L, Rampioni G, Di Stefano V, Zennaro E. Dual role of response regulator StyR in styrene catabolism regulation. Appl Environ Microbiol. 2005;71:5411-9 pubmed
    ..We suggest that the cellular levels of phosphorylated StyR, as determined by StyS sensor kinase activity, and the interplay of this molecule with IHF modulate the activity of the promoter in different growth conditions. ..
  31. Jeong H, Kim S, Lim M, Kim K, Choi S. Direct interaction between quorum-sensing regulator SmcR and RNA polymerase is mediated by integration host factor to activate vvpE encoding elastase in Vibrio vulnificus. J Biol Chem. 2010;285:9357-66 pubmed publisher
    ..Collectively, the results proposed a model whereby IHF positions SmcR to contact RNAP by looping the vvpE regulatory DNA, thus allowing precise control of the expression level of VvpE during the pathogenesis of V. vulnificus. ..
  32. Ryan V, Grimwade J, Camara J, Crooke E, Leonard A. Escherichia coli prereplication complex assembly is regulated by dynamic interplay among Fis, IHF and DnaA. Mol Microbiol. 2004;51:1347-59 pubmed
  33. Aeling K, Opel M, Steffen N, Tretyachenko Ladokhina V, Hatfield G, Lathrop R, et al. Indirect recognition in sequence-specific DNA binding by Escherichia coli integration host factor: the role of DNA deformation energy. J Biol Chem. 2006;281:39236-48 pubmed
  34. Gustave J, Jurcisek J, McCoy K, Goodman S, Bakaletz L. Targeting bacterial integration host factor to disrupt biofilms associated with cystic fibrosis. J Cyst Fibros. 2013;12:384-9 pubmed publisher
    ..These data support further investigation of IHF as a potential therapeutic target for patients with CF. ..
  35. Aviv M, Giladi H, Schreiber G, Oppenheim A, Glaser G. Expression of the genes coding for the Escherichia coli integration host factor are controlled by growth phase, rpoS, ppGpp and by autoregulation. Mol Microbiol. 1994;14:1021-31 pubmed
    ..All three sites show low binding affinity to IHF suggesting that autoregulation can take place only after sufficiently high levels of IHF accumulate in the cell. ..
  36. Bonnefoy E, Rouviere Yaniv J. HU and IHF, two homologous histone-like proteins of Escherichia coli, form different protein-DNA complexes with short DNA fragments. EMBO J. 1991;10:687-96 pubmed
    ..coli (IHF) form different structures with the same DNA fragments. Moreover, HU seems to enhance the DNA-binding capacity of IHF to a DNA fragment which does not contain its consensus sequence. ..
  37. Granston A, Nash H. Characterization of a set of integration host factor mutants deficient for DNA binding. J Mol Biol. 1993;234:45-59 pubmed
    ..We discuss the positions of the mutant amino acid residues as they relate to a proposed molecular model of an IHF:DNA complex. ..
  38. 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. ..
  39. Rowe S, Hodson N, Griffiths G, Roberts I. Regulation of the Escherichia coli K5 capsule gene cluster: evidence for the roles of H-NS, BipA, and integration host factor in regulation of group 2 capsule gene clusters in pathogenic E. coli. J Bacteriol. 2000;182:2741-5 pubmed
    ..These results indicate that a complex regulatory network involving a number of global regulators exists for the control of expression of group 2 capsules in E. coli. ..
  40. Dworkin J, Ninfa A, Model P. A protein-induced DNA bend increases the specificity of a prokaryotic enhancer-binding protein. Genes Dev. 1998;12:894-900 pubmed
    ..These opposite effects have the consequence of increasing the specificity of activation of a promoter that is susceptible to regulation by proteins bound to a distal site. ..
  41. Rice P. Making DNA do a U-turn: IHF and related proteins. Curr Opin Struct Biol. 1997;7:86-93 pubmed
    ..In addition to the crystal structure of IHF bound to DNA, the past year has seen a number of advances in the understanding of the interactions of these proteins with DNA in solution. ..
  42. Mengeritsky G, Goldenberg D, Mendelson I, Giladi H, Oppenheim A. Genetic and biochemical analysis of the integration host factor of Escherichia coli. J Mol Biol. 1993;231:646-57 pubmed
    ..The binding of IHF to DNA is probably not restricted to one domain, but requires the co-operative participation of a number of regions of the protein. ..
  43. Dworkin J, Jovanovic G, Model P. Role of upstream activation sequences and integration host factor in transcriptional activation by the constitutively active prokaryotic enhancer-binding protein PspF. J Mol Biol. 1997;273:377-88 pubmed
    ..These data, taken together, support the model that a precise promoter geometry is necessary for IHF to positively regulate transcription and that IHF may act to prevent activation from inappropriately spaced upstream sites. ..
  44. Flamm E, Weisberg R. Primary structure of the hip gene of Escherichia coli and of its product, the beta subunit of integration host factor. J Mol Biol. 1985;183:117-28 pubmed
    ..A hip missense mutation that replaces a completely conserved glycine with aspartate has a null phenotype, suggesting that the conserved regions are functionally important...
  45. Moitoso de Vargas L, Kim S, Landy A. DNA looping generated by DNA bending protein IHF and the two domains of lambda integrase. Science. 1989;244:1457-61 pubmed
    ..The bivalent DNA binding protein is positioned at high affinity sites and directed, by a DNA bending protein, to interactions with distant lower affinity sites. Assembly of this complex is independent of protein-protein interactions. ..
  46. Yang C, Nash H. The interaction of E. coli IHF protein with its specific binding sites. Cell. 1989;57:869-80 pubmed
  47. Vivas P, Kuznetsov S, Ansari A. New insights into the transition pathway from nonspecific to specific complex of DNA with Escherichia coli integration host factor. J Phys Chem B. 2008;112:5997-6007 pubmed publisher
  48. Santos P, Leoni L, di Bartolo I, Zennaro E. Integration host factor is essential for the optimal expression of the styABCD operon in Pseudomonas fluorescens ST. Res Microbiol. 2002;153:527-36 pubmed
  49. Vivas P, Velmurugu Y, Kuznetsov S, Rice P, Ansari A. Mapping the transition state for DNA bending by IHF. J Mol Biol. 2012;418:300-15 pubmed publisher
  50. Holbrook J, Tsodikov O, Saecker R, Record M. Specific and non-specific interactions of integration host factor with DNA: thermodynamic evidence for disruption of multiple IHF surface salt-bridges coupled to DNA binding. J Mol Biol. 2001;310:379-401 pubmed
  51. Ali B, Amit R, Braslavsky I, Oppenheim A, Gileadi O, Stavans J. Compaction of single DNA molecules induced by binding of integration host factor (IHF). Proc Natl Acad Sci U S A. 2001;98:10658-63 pubmed
    ..Our findings support the long-held view that IHF and other histone-like proteins play an important role in shaping the long-scale structure of the bacterial nucleoid. ..
  52. Saecker R, Record M. Protein surface salt bridges and paths for DNA wrapping. Curr Opin Struct Biol. 2002;12:311-9 pubmed
  53. Lee E, Hales L, Gumport R, Gardner J. The isolation and characterization of mutants of the integration host factor (IHF) of Escherichia coli with altered, expanded DNA-binding specificities. EMBO J. 1992;11:305-13 pubmed
    ..We discuss the possible mechanisms of suppression by the mutants in terms of a model of the IHF-DNA complex proposed by Yang and Nash [Cell, 57, 869-880 (1989)]. ..
  54. Vander Meulen K, Saecker R, Record M. Formation of a wrapped DNA-protein interface: experimental characterization and analysis of the large contributions of ions and water to the thermodynamics of binding IHF to H' DNA. J Mol Biol. 2008;377:9-27 pubmed publisher
    ..7+/-0.4 at constant KCl activity, indicating the net release of ca. 150 H(2)O molecules from anionic surface. ..
  55. 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. ..
  56. Corcoran C, Dorman C. DNA relaxation-dependent phase biasing of the fim genetic switch in Escherichia coli depends on the interplay of H-NS, IHF and LRP. Mol Microbiol. 2009;74:1071-82 pubmed publisher
  57. 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. ..
  58. Lorenz M, Diekmann S. Quantitative distance information on protein-DNA complexes determined in polyacrylamide gels by fluorescence resonance energy transfer. Electrophoresis. 2001;22:990-8 pubmed
    ..The measured Forster transfer efficiency allows us to deduce information on the overall shape and the DNA bending angle in the complex. ..
  59. Hill S, Samuels D, Nielsen C, Knight S, Pagotto F, Dillon J. Integration host factor interactions with Neisseria gene sequences: correlation between predicted binding sites and in vitro binding of Neisseria -derived IHF protein. Mol Cell Probes. 2002;16:153-8 pubmed
    ..The results show a positive correlation between the identification of a predicted Neisseria IHF binding site and in vitro binding of Neisseria -derived IHF protein. ..
  60. Ryan V, Grimwade J, Nievera C, Leonard A. IHF and HU stimulate assembly of pre-replication complexes at Escherichia coli oriC by two different mechanisms. Mol Microbiol. 2002;46:113-24 pubmed
    ..HU did not redistribute DnaA, but suppressed binding specifically at I3. These results suggest that different pathways mediated by bacterial chromatin proteins exist to regulate pre-RC assembly and unwind oriC. ..