Indirect Recognition in Sequence-specific DNA Binding by Escherichia coli Integration Host Factor

Integration host factor (IHF) is a bacterial histone-like protein whose primary biological role is to condense the bacterial nucleoid and to constrain DNA supercoils. It does so by binding in a sequence-independent manner throughout the genome. However, unlike other structurally related bacterial histone-like proteins, IHF has evolved a sequence-dependent, high affinity DNA-binding motif. The high affinity binding sites are important for the regulation of a wide range of cellular processes. A remarkable feature of IHF is that it employs an indirect readout mechanism to bind and wrap DNA at both the nonspecific and high affinity (sequence-dependent) DNA sites. In this study we assessed the contributions of pre-formed and protein-induced DNA conformations to the energetics of IHF binding. Binding energies determined experimentally were compared with energies predicted for the IHF-induced deformation of the DNA helix (DNA deformation energy) in the IHF-DNA complex. Combinatorial sets of de novo DNA sequences were designed to systematically evaluate the influence of sequence-dependent structural characteristics of the conserved IHF recognition elements of the consensus DNA sequence. We show that IHF recognizes pre-formed conformational characteristics of the consensus DNA sequence at high affinity sites, whereas at all other sites relative affinity is determined by the deformational energy required for nearest-neighbor base pairs to adopt the DNA structure of the bound DNA-IHF complex.

[1]  R. Weisberg,et al.  Overproduction of Escherichia coli integration host factor, a protein with nonidentical subunits , 1987, Journal of bacteriology.

[2]  W. McClure,et al.  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). , 1990, Nucleic acids research.

[3]  I. Beacham,et al.  Transcriptional co‐activation at the ansB promoters: involvement of the activating regions of CRP and FNR when bound in tandem , 1995, Molecular microbiology.

[4]  P. Model,et al.  Analysis of the proteins and cis-acting elements regulating the stress-induced phage shock protein operon. , 1995, Nucleic acids research.

[5]  M. Record,et al.  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. , 2001, Journal of molecular biology.

[6]  G. Unden,et al.  Growth phase-dependent regulation of nuoA-N expression in Escherichia coli K-12 by the Fis protein: upstream binding sites and bioenergetic significance , 1999, Molecular and General Genetics MGG.

[7]  E. Yagil,et al.  The Integration Host Factor (IHF) Affects the Expression of the Phosphate-Binding Protein and of Alkaline Phosphatase in Escherichia coli , 1999, Current Microbiology.

[8]  I. Epstein,et al.  Cooperative and non-cooperative binding of large ligands to a finite one-dimensional lattice. A model for ligand-oligonucleotide interactions. , 1978, Biophysical chemistry.

[9]  M. Record,et al.  Protein surface salt bridges and paths for DNA wrapping. , 2002, Current opinion in structural biology.

[10]  S. Sewitz,et al.  The positive and negative regulation of Tn10 transposition by IHF is mediated by structurally asymmetric transposon arms. , 2003, Nucleic acids research.

[11]  Samuel Selvaraj,et al.  Intermolecular and intramolecular readout mechanisms in protein-DNA recognition. , 2004, Journal of molecular biology.

[12]  J. Geiselmann,et al.  In vivo interaction of the Escherichia coli integration host factor with its specific binding sites. , 1995, Nucleic acids research.

[13]  Phoebe A Rice,et al.  Integration host factor: putting a twist on protein-DNA recognition. , 2003, Journal of molecular biology.

[14]  G W Hatfield,et al.  Inhibition of DNA Supercoiling-dependent Transcriptional Activation by a Distant B-DNA to Z-DNA Transition* , 1999, The Journal of Biological Chemistry.

[15]  宁北芳,et al.  疟原虫var基因转换速率变化导致抗原变异[英]／Paul H, Robert P, Christodoulou Z, et al//Proc Natl Acad Sci U S A , 2005 .

[16]  G. Jovanovic,et al.  PspF and IHF bind co‐operatively in the psp promoter‐regulatory region of Escherichia coli , 1997, Molecular microbiology.

[17]  H. Nash,et al.  Role of Escherichia coli IHF protein in lambda site-specific recombination. A mutational analysis of binding sites. , 1986, Journal of molecular biology.

[18]  K. Drlica,et al.  Histonelike proteins of bacteria. , 1987, Microbiological reviews.

[19]  I. Blomfield,et al.  Integration host factor stimulates both FimB‐ and FimE‐mediated site‐specific DNA inversion that controls phase variation of type 1 fimbriae expression in Escherichia coli , 1997, Molecular microbiology.

[20]  A. Kornberg,et al.  Opening of the replication origin of Escherichia coli by DnaA protein with protein HU or IHF. , 1992, The Journal of biological chemistry.

[21]  J. Demoss,et al.  Structure modification induced in the narG promoter by binding of integration host factor and NARL-P , 1996, Journal of bacteriology.

[22]  Phoebe A Rice,et al.  Crystal Structure of an IHF-DNA Complex: A Protein-Induced DNA U-Turn , 1996, Cell.

[23]  Robert M. Blumenthal,et al.  Activation from a Distance: Roles of Lrp and Integration Host Factor in Transcriptional Activation ofgltBDF , 2001, Journal of bacteriology.

[24]  A. Sirko,et al.  The role of integration host factor In gene expression in Escherichia coli , 1992, Molecular microbiology.

[25]  A. Ninfa,et al.  A protein-induced DNA bend increases the specificity of a prokaryotic enhancer-binding protein. , 1998, Genes & development.

[26]  B. Magasanik,et al.  Role of integration host factor in the regulation of the glnHp2 promoter of Escherichia coli. , 1991, Proceedings of the National Academy of Sciences of the United States of America.

[27]  M. Anjum,et al.  Regulation of the ndh gene of Escherichia coli by integration host factor and a novel regulator, Arr. , 1997, Microbiology.

[28]  M. Freundlich,et al.  Integration host factor binds specifically to sites in the ilvGMEDA operon in Escherichia coli. , 1988, Journal of molecular biology.

[29]  J. Geiselmann,et al.  A quantitative UV laser footprinting analysis of the interaction of IHF with specific binding sites: re-evaluation of the effective concentration of IHF in the cell. , 1998, Journal of molecular biology.

[30]  GusfieldDan.  Introduction to the IEEE/ACM Transactions on Computational Biology and Bioinformatics , 2004 .

[31]  A. Böck,et al.  Regulated expression in vitro of genes coding for formate hydrogenlyase components of Escherichia coli. , 1994, The Journal of biological chemistry.

[32]  V. Stewart,et al.  In vivo requirement of integration host factor for nar (nitrate reductase) operon expression in Escherichia coli K-12. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[33]  P. V. von Hippel,et al.  Theoretical aspects of DNA-protein interactions: co-operative and non-co-operative binding of large ligands to a one-dimensional homogeneous lattice. , 1974, Journal of molecular biology.

[34]  George E. P. Box,et al.  FITTING EMPIRICAL DATA * , 1960 .

[35]  R. Gumport,et al.  Determining the DNA sequence elements required for binding integration host factor to two different target sites , 1994, Journal of bacteriology.

[36]  Craig J. Benham,et al.  Activation of Gene Expression by a Novel DNA Structural Transmission Mechanism That Requires Supercoiling-induced DNA Duplex Destabilization in an Upstream Activating Sequence* , 1998, The Journal of Biological Chemistry.

[37]  I. Blomfield,et al.  The molecular basis for the specificity of fimE in the phase variation of type 1 fimbriae of Escherichia coli K‐12 , 1999, Molecular microbiology.

[38]  M. Record,et al.  Analytic binding isotherms describing competitive interactions of a protein ligand with specific and nonspecific sites on the same DNA oligomer. , 2001, Biophysical journal.

[39]  Anca M. Segall,et al.  In Vitro Selection of Integration Host Factor Binding Sites , 1999, Journal of bacteriology.

[40]  H. Nash,et al.  Comparison of protein binding to DNA in vivo and in vitro: defining an effective intracellular target. , 1995, The EMBO journal.

[41]  D. Baker,et al.  Protein–DNA binding specificity predictions with structural models , 2005, Nucleic acids research.

[42]  Leonardo Pardo,et al.  Binding of proteins to the minor groove of DNA: What are the structural and energetic determinants for kinking a basepair step? , 2003, J. Comput. Chem..

[43]  S Brunak,et al.  Genome organisation and chromatin structure in Escherichia coli. , 2001, Biochimie.

[44]  A. Oppenheim,et al.  Genetic and biochemical analysis of the integration host factor of Escherichia coli. , 1993, Journal of molecular biology.

[45]  D. Friedman,et al.  Integration host factor: A protein for all reasons , 1988, Cell.

[46]  T. Leisinger,et al.  The Escherichia coli ssuEADCB Gene Cluster Is Required for the Utilization of Sulfur from Aliphatic Sulfonates and Is Regulated by the Transcriptional Activator Cbl* , 1999, The Journal of Biological Chemistry.

[47]  G. W. Hatfield,et al.  Activation of transcription initiation from a stable RNA promoter by a Fis protein‐mediated DNA structural transmission mechanism , 2004, Molecular microbiology.

[48]  K. A. Walker,et al.  Deletion analysis of the fis promoter region in Escherichia coli: antagonistic effects of integration host factor and Fis , 1997, Journal of bacteriology.

[49]  A. Travers.  DNA–protein interactions: IHF - the master bender , 1997, Current Biology.

[50]  S. Diekmann,et al.  Global structure similarities of intact and nicked DNA complexed with IHF measured in solution by fluorescence resonance energy transfer. , 1999, Nucleic acids research.

[51]  O. Gileadi,et al.  Compaction of single DNA molecules induced by binding of integration host factor (IHF) , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[52]  V. Zhurkin,et al.  DNA sequence-dependent deformability deduced from protein-DNA crystal complexes. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[53]  A M Gronenborn,et al.  Minor groove-binding architectural proteins: structure, function, and DNA recognition. , 1998, Annual review of biophysics and biomolecular structure.

[54]  M. Freundlich,et al.  In vitro interactions of integration host factor with the ompF promoter-regulatory region of Escherichia coli , 2004, Molecular and General Genetics MGG.

[55]  M. Araúzo-Bravo,et al.  Sequence-dependent conformational energy of DNA derived from molecular dynamics simulations: toward understanding the indirect readout mechanism in protein-DNA recognition. , 2005, Journal of the American Chemical Society.

[56]  Chris Sander.  The Journal Bioinformatics, key medium for computational biology , 2002, Bioinform..

[57]  F. Young.  Biochemistry , 1955, The Indian Medical Gazette.

[58]  Samuel Selvaraj,et al.  Role of inter and intramolecular interactions in protein-DNA recognition. , 2005, Gene.

[59]  Roberto Kolter,et al.  The dps promoter is activated by OxyR during growth and by IHF and σs in stationary phase , 1994, Molecular microbiology.

[60]  M. Freundlich,et al.  Integration host factor binds specifically to multiple sites in the ompB promoter of Escherichia coli and inhibits transcription , 1991, Journal of bacteriology.

[61]  R. Gunsalus,et al.  Anaerobic regulation of the Escherichia coli dmsABC operon requires the molybdate‐responsive regulator ModE , 1998, Molecular microbiology.

[62]  G. W. Hatfield,et al.  Transcriptional activation by protein-induced DNA bending: evidence for a DNA structural transmission model. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[63]  A. Sirko,et al.  Integration host factor positively regulates cysJIH transcription , 1998, Molecular and General Genetics MGG.

[64]  R. Gumport,et al.  Examining the contribution of a dA+dT element to the conformation of Escherichia coli integration host factor-DNA complexes. , 1996, Nucleic acids research.

[65]  A. Sirko,et al.  Selected phenotypes of ihf mutants of Escherichia coli. , 1998, Biochimie.

[66]  G. W. Hatfield,et al.  DNA topology-mediated control of global gene expression in Escherichia coli. , 2002, Annual review of genetics.

[67]  R. Gumport,et al.  The specific binding of Escherichia coli integration host factor involves both major and minor grooves of DNA. , 1995, Biochemistry.

[68]  G. Sawers,et al.  Integration host factor is required for anaerobic pyruvate induction of pfl operon expression in Escherichia coli , 1993, Journal of bacteriology.

[69]  P. Datta,et al.  Catabolite gene activator protein and integration host factor act in concert to regulate tdc operon expression in Escherichia coli , 1992, Journal of bacteriology.

[70]  S. Busby,et al.  Independent regulation of the divergent Escherichia coli nrfA and acsP1 promoters by a nucleoprotein assembly at a shared regulatory region , 2002, Molecular microbiology.

[71]  P. Rice,et al.  Making DNA do a U-turn: IHF and related proteins. , 1997, Current opinion in structural biology.

[72]  M. Freundlich,et al.  Integration host factor is a negative effector of in vivo and in vitro expression of ompC in Escherichia coli , 1990, Journal of bacteriology.