Fast Prediction of DNA Melting Bubbles Using DNA Thermodynamic Stability

DNA melting bubbles are the basis of many DNA-protein interactions, such as those in regulatory DNA regions driving gene expression, DNA replication and bacterial horizontal gene transfer. Bubble formation is affected by DNA duplex stability and thermally induced duplex destabilization (TIDD). Although prediction of duplex stability with the nearest neighbor (NN) method is much faster than prediction of TIDD with the Peyrard-Bishop-Dauxois (PBD) model, PBD predicted TIDD defines regulatory DNA regions with higher accuracy and detail. Here, we considered that PBD predicted TIDD is inherently related to the intrinsic duplex stabilities of destabilization regions. We show by regression modeling that NN duplex stabilities can be used to predict TIDD almost as accurately as is predicted with PBD. Predicted TIDD is in fact ascribed to non-linear transformation of NN duplex stabilities in destabilization regions as well as effects of neighboring regions relative to destabilization size. Since the prediction time of our models is over six orders of magnitude shorter than that of PBD, the models present an accessible tool for researchers. TIDD can be predicted on our webserver at http://tidd.immt.eu.

[1]  Kathleen Marchal,et al.  Use of structural DNA properties for the prediction of transcription-factor binding sites in Escherichia coli , 2010, Nucleic Acids Res..

[2]  E. Lanka,et al.  The origin of conjugative IncP plasmid transfer: interaction with plasmid-encoded products and the nucleotide sequence at the relaxation site. , 1988, Biochimica et biophysica acta.

[3]  A. C. Evans,et al.  Distance-dependent duplex DNA destabilization proximal to G-quadruplex/i-motif sequences , 2013, Nucleic acids research.

[4]  M. E. Farías,et al.  Conjugal transfer of plasmid pMV158: uncoupling of the pMV158 origin of transfer from the mobilization gene mobM, and modulation of pMV158 transfer in Escherichia coli mediated by IncP plasmids. , 2000, Microbiology.

[5]  Siddhartha Roy,et al.  Indirect read-out of the promoter DNA by RNA polymerase in the closed complex , 2012, Nucleic acids research.

[6]  A. Usheva,et al.  DNA breathing dynamics distinguish binding from nonbinding consensus sites for transcription factor YY1 in cells , 2012, Nucleic acids research.

[7]  A. R. Bishop,et al.  Sequence-specific thermal fluctuations identify start sites for DNA transcription , 2003, cond-mat/0309157.

[8]  G. del Solar,et al.  Lagging-strand origins of the promiscuous plasmid pMV158: physical and functional characterization. , 1995, Microbiology.

[9]  A. Heeger,et al.  Nature of the open state in long polynucleotide double helices: possibility of soliton excitations. , 1980, Proceedings of the National Academy of Sciences of the United States of America.

[10]  M. Bjornsti,et al.  Cellular Strategies for Regulating DNA Supercoiling: A Single-Molecule Perspective , 2010, Cell.

[11]  R. Mann,et al.  Origins of specificity in protein-DNA recognition. , 2010, Annual review of biochemistry.

[12]  R. Metzler,et al.  Bubble dynamics in DNA , 2003, cond-mat/0305049.

[13]  Kathleen Marchal,et al.  DNA Structural Properties in the Classification of Genomic Transcription Regulation Elements , 2012, Bioinformatics and biology insights.

[14]  D. Angelov,et al.  Experimental and theoretical studies of sequence effects on the fluctuation and melting of short DNA molecules , 2008, Journal of physics. Condensed matter : an Institute of Physics journal.

[15]  S. W. Matson,et al.  Escherichia coli DNA helicase I catalyzes a site- and strand-specific nicking reaction at the F plasmid oriT. , 1991, The Journal of biological chemistry.

[16]  Johannes-Geert Hagmann,et al.  Can one predict DNA transcription start sites by studying bubbles? , 2005, Physical review letters.

[17]  Fangping Mu,et al.  Binding of Nucleoid-Associated Protein Fis to DNA Is Regulated by DNA Breathing Dynamics , 2013, PLoS Comput. Biol..

[18]  Maxim D. Frank-Kamenetskii,et al.  Sequence-Dependent Basepair Opening in DNA Double Helix , 2006 .

[19]  Steven Hahn,et al.  Structure and mechanism of the RNA polymerase II transcription machinery , 2004, Nature Structural &Molecular Biology.

[20]  David Bikard,et al.  Folded DNA in Action: Hairpin Formation and Biological Functions in Prokaryotes , 2010, Microbiology and Molecular Biology Reviews.

[21]  Manju Bansal,et al.  A novel method for prokaryotic promoter prediction based on DNA stability , 2005, BMC Bioinformatics.

[22]  D. Coman,et al.  Base Pair Opening in Three DNA-unwinding Elements* , 2005, Journal of Biological Chemistry.

[23]  Ashutosh Gupta,et al.  The importance of being supercoiled: how DNA mechanics regulate dynamic processes. , 2012, Biochimica et biophysica acta.

[24]  L. Movileanu,et al.  Temperature dependence of the Raman spectrum of DNA. II. Raman signatures of premelting and melting transitions of poly(dA).poly(dT) and comparison with poly(dA-dT).poly(dA-dT). , 2002, Biopolymers.

[25]  Michael G. Poirier,et al.  The flexibility of locally melted DNA , 2009, Nucleic acids research.

[26]  S. Darst,et al.  Structural Basis for Promoter −10 Element Recognition by the Bacterial RNA Polymerase σ Subunit , 2011, Cell.

[27]  M. Lucas,et al.  Recognition and processing of the origin of transfer DNA by conjugative relaxase TrwC , 2003, Nature Structural Biology.

[28]  Maxim D. Frank-Kamenetskii,et al.  Biophysics of the DNA molecule , 1997 .

[29]  D. Bastia,et al.  Reconstitution of F Factor DNA Replication in Vitro with Purified Proteins* , 2004, Journal of Biological Chemistry.

[30]  อนิรุธ สืบสิงห์,et al.  Data Mining Practical Machine Learning Tools and Techniques , 2014 .

[31]  L. Vielva,et al.  Dynamics of the IncW genetic backbone imply general trends in conjugative plasmid evolution. , 2006, FEMS microbiology reviews.

[32]  Alan R Bishop,et al.  DNA dynamically directs its own transcription initiation. , 2004, Nucleic acids research.

[33]  Sang Wook Yoo,et al.  Toward a Detailed Description of the Thermally Induced Dynamics of the Core Promoter , 2009, PLoS Comput. Biol..

[34]  Ian Witten,et al.  Data Mining , 2000 .

[35]  Julio Collado-Vides,et al.  RegulonDB v8.0: omics data sets, evolutionary conservation, regulatory phrases, cross-validated gold standards and more , 2012, Nucleic Acids Res..

[36]  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.

[37]  J. G. Snijders,et al.  Hydrogen Bonding in DNA Base Pairs: Reconciliation of Theory and Experiment , 2000 .

[38]  Christopher M Thomas,et al.  Nucleotide sequence of the region of the origin of replication of the broad host range plasmid RK2 , 2004, Molecular and General Genetics MGG.

[39]  M. Guéron,et al.  A single mode of DNA base-pair opening drives imino proton exchange , 1987, Nature.

[40]  Yvan Saeys,et al.  Large-scale structural analysis of the core promoter in mammalian and plant genomes , 2005, Nucleic acids research.

[41]  Manju Bansal,et al.  Structural properties of promoters: similarities and differences between prokaryotes and eukaryotes , 2005, Nucleic acids research.

[42]  Sarah L. Westcott,et al.  Structural Basis of DNA Replication Origin Recognition by an ORC Protein , 2007, Science.

[43]  R. Meyer.  Replication and conjugative mobilization of broad host-range IncQ plasmids. , 2009, Plasmid.

[44]  R. Metzler,et al.  Supercoiling induces denaturation bubbles in circular DNA. , 2010, Physical review letters.

[45]  S. Busby,et al.  The regulation of bacterial transcription initiation , 2004, Nature Reviews Microbiology.

[46]  Bishop,et al.  Entropy-driven DNA denaturation. , 1993, Physical review. E, Statistical physics, plasmas, fluids, and related interdisciplinary topics.

[47]  D. Reinberg,et al.  Mechanism of ATP-dependent promoter melting by transcription factor IIH. , 2000, Science.

[48]  T. Strick,et al.  Homologous pairing in stretched supercoiled DNA. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

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

[50]  Shuigeng Zhou,et al.  A pattern-based nearest neighbor search approach for promoter prediction using DNA structural profiles , 2009, Bioinform..

[51]  Anindya Dutta,et al.  DNA replication in eukaryotic cells. , 2002, Annual review of biochemistry.

[52]  M. Frank-Kamenetskii,et al.  Stacked-unstacked equilibrium at the nick site of DNA. , 2004, Journal of molecular biology.

[53]  Sarah A. Harris,et al.  Atomistic simulations reveal bubbles, kinks and wrinkles in supercoiled DNA , 2011, Nucleic acids research.

[54]  N. Horton,et al.  Early interrogation and recognition of DNA sequence by indirect readout. , 2008, Structure.

[55]  Fernando de la Cruz,et al.  Conjugative DNA metabolism in Gram-negative bacteria. , 2010, FEMS microbiology reviews.

[56]  Grégoire Altan-Bonnet,et al.  Bubble dynamics in double-stranded DNA. , 2003, Physical review letters.

[57]  S. Bolland,et al.  Structural and functional analysis of the origin of conjugal transfer of the broad-host-range IneW plasmid R388 and comparison with the related IncN plasmid R46 , 1991, Molecular and General Genetics MGG.

[58]  P. Lau,et al.  The mobilization and origin of transfer regions of a Thiobacillus ferrooxidans plasmid: relatedness to plasmids RSF1010 and pSC101 , 1990, Molecular microbiology.

[59]  D. Angelov,et al.  Guanine radical chemistry reveals the effect of thermal fluctuations in gene promoter regions , 2011, Nucleic acids research.

[60]  C. Benham,et al.  Sites of predicted stress-induced DNA duplex destabilization occur preferentially at regulatory loci. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[61]  Yvan Saeys,et al.  Generic eukaryotic core promoter prediction using structural features of DNA. , 2008, Genome research.

[62]  Fang Liu,et al.  Speed-up of DNA melting algorithm with complete nearest neighbor properties. , 2003, Biopolymers.

[63]  J. SantaLucia,et al.  The thermodynamics of DNA structural motifs. , 2004, Annual review of biophysics and biomolecular structure.

[64]  Manuel Espinosa,et al.  Plasmids Replication and Control of Circular Bacterial , 1998 .

[65]  G. Kalosakas,et al.  Targets of DNA-binding proteins in bacterial promoter regions present enhanced probabilities for spontaneous thermal openings , 2011, Physical biology.

[66]  R J Roberts,et al.  On base flipping , 1995, Cell.

[67]  Alan R. Bishop,et al.  DNA dynamics play a role as a basal transcription factor in the positioning and regulation of gene transcription initiation , 2009, Nucleic acids research.