We analyzed the structural behavior of DNA complexed with regulatory proteins and the nucleosome core particle (NCP). The three-dimensional structures of almost 25 thousand dinucleotide steps from more than 500 sequentially non-redundant crystal structures were classified by using DNA structural alphabet CANA (Conformational Alphabet of Nucleic Acids) and associations between ten CANA letters and sixteen dinucleotide sequences were investigated. The associations showed features discriminating between specific and non-specific binding of DNA to proteins. Important is the specific role of two DNA structural forms, A-DNA, and BII-DNA, represented by the CANA letters AAA and BB2: AAA structures are avoided in non-specific NCP complexes, where the wrapping of the DNA duplex is explained by the periodic occurrence of BB2 every 10.3 steps. In both regulatory and NCP complexes, the extent of bending of the DNA local helical axis does not influence proportional representation of the CANA alphabet letters, namely the relative incidences of AAA and BB2 remain constant in bent and straight duplexes.

Institute of Biotechnology of the Czech Academy of Sciences BIOCEV Průmyslová 595 CZ 252 50 Vestec Prague West Czech Republic

Laboratory of Informatics and Chemistry Faculty of Chemical Technology University of Chemistry and Technology Prague Technická 5 CZ 166 28 Prague Czech Republic

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Watson J.D., Crick F.H.C. A structure for deoxyribose nucleic acid. Nature. 1953;171:737–738. doi: 10.1038/171737a0. PubMed DOI

Rohs R., Jin X., West S.M., Joshi R., Honig B., Mann R.S. Origins of specificity in protein-DNA recognition. Annu. Rev. Biochem. 2010;79:233–269. doi: 10.1146/annurev-biochem-060408-091030. PubMed DOI PMC

Parker S.C., Hansen L., Abaan H.O., Tullius T.D., Margulies E.H. Local DNA topography correlates with functional noncoding regions of the human genome. Science. 2009;324:389–392. doi: 10.1126/science.1169050. PubMed DOI PMC

Unger R., Harel D., Wherland S., Sussman J.L. A 3D building blocks approach to analyzing and predicting structure of proteins. Proteins. 1989;5:355–373. doi: 10.1002/prot.340050410. PubMed DOI

Levitt M. Accurate modeling of protein conformation by automatic segment matching. J. Mol. Biol. 1992;226:507–533. doi: 10.1016/0022-2836(92)90964-L. PubMed DOI

Joseph A.P., Agarwal G., Mahajan S., Gelly J.-C., Swapna L.S., Offmann B., Cadet F., Bornot A., Tyagi M., Valadié H., et al. A short survey on protein blocks. Biophys. Rev. 2010;2:137–145. doi: 10.1007/s12551-010-0036-1. PubMed DOI PMC

Cech P., Kukal J., Cerny J., Schneider B., Svozil D. Automatic workflow for the classification of local DNA conformations. BMC Bioinform. 2013;14:205. doi: 10.1186/1471-2105-14-205. PubMed DOI PMC

Černý J., Božíková P., Schneider B. DNATCO: Assignment of DNA conformers at dnatco.org. Nucleic Acids Res. 2016;44:W284–W287. doi: 10.1093/nar/gkw381. PubMed DOI PMC

Schneider B., Cerny J., Svozil D., Cech P., Gelly J.C., de Brevern A.G. Bioinformatic analysis of the protein/DNA interface. Nucleic Acids Res. 2014;42:3381–3394. doi: 10.1093/nar/gkt1273. PubMed DOI PMC

Patikoglou G., Burley S.K. Eukaryotic transcription factor-DNA complexes. Annu. Rev. Biophys. Biomol. Struct. 1997;26:289–325. doi: 10.1146/annurev.biophys.26.1.289. PubMed DOI

Cui F., Zhurkin V.B. Rotational positioning of nucleosomes facilitates selective binding of p53 to response elements associated with cell cycle arrest. Nucleic Acids Res. 2014;42:836–847. doi: 10.1093/nar/gkt943. PubMed DOI PMC

Laptenko O., Beckerman R., Freulich E., Prives C. P53 binding to nucleosomes within the p21 promoter in vivo leads to nucleosome loss and transcriptional activation. Proc. Natl. Acad. Sci. USA. 2011;108:10385–10390. doi: 10.1073/pnas.1105680108. PubMed DOI PMC

Joseph S.R., Pálfy M., Hilbert L., Kumar M., Karschau J., Zaburdaev V., Shevchenko A., Vastenhouw N.L. Competition between histone and transcription factor binding regulates the onset of transcription in zebrafish embryos. eLife. 2017;6:e23326. doi: 10.7554/eLife.23326. PubMed DOI PMC

Berman H.M., Westbrook J., Feng Z., Iype L., Schneider B., Zardecki C. The nucleic acid database. Acta Crystallogr. D. 2002;58:899–907. doi: 10.1107/S0907444902003451. PubMed DOI

Richmond T.J., Davey C.A. The structure of DNA in the nucleosome core. Nature. 2003;423:145–150. doi: 10.1038/nature01595. PubMed DOI

Schneider B., Gelly J.C., de Brevern A.G., Cerny J. Local dynamics of proteins and DNA evaluated from crystallographic b factors. Acta Crystallogr. D. 2014;70:2413–2419. doi: 10.1107/S1399004714014631. PubMed DOI PMC

R Core Team R: A language and environment for statistical computing. 2016.

Agresti A. An Introduction to Categorical Data Analysis. Wiley; Hoboken, NJ, USA: 2007.

Xu F., Olson W.K. DNA architecture, deformability, and nucleosome positioning. J. Biomol. Struct. Dyn. 2010;27:725–739. doi: 10.1080/073911010010524943. PubMed DOI PMC

Cui F., Zhurkin V.B. Structure-based analysis of DNA sequence patterns guiding nucleosome positioning in vitro. J. Biomol. Struct. Dyn. 2010;27:821–841. doi: 10.1080/073911010010524947. PubMed DOI PMC

Gouge J., Satia K., Guthertz N., Widya M., Thompson A.J., Cousin P., Dergai O., Hernandez N., Vannini A. Redox signaling by the RNA polymerase III TFIIB-related factor Brf2. Cell. 2015;163:1375–1387. doi: 10.1016/j.cell.2015.11.005. PubMed DOI PMC

Olson W.K., Zhurkin V.B. Working the kinks out of nucleosomal DNA. Curr. Opin. Struct. Biol. 2011;21:348–357. doi: 10.1016/j.sbi.2011.03.006. PubMed DOI PMC

Blanchet C., Pasi M., Zakrzewska K., Lavery R. Curves+ web server for analyzing and visualizing the helical, backbone and groove parameters of nucleic acid structures. Nucleic Acids Res. 2011;39:W68–W73. doi: 10.1093/nar/gkr316. PubMed DOI PMC

Zaret K.S., Caravaca J.M., Tulin A., Sekiya T. Nuclear mobility and mitotic chromosome binding: Similarities between pioneer transcription factor foxa and linker histone H1. Cold Spring Harb. Symp. Quant. Biol. 2010;75:219–226. doi: 10.1101/sqb.2010.75.061. PubMed DOI

Magnani L., Eeckhoute J., Lupien M. Pioneer factors: Directing transcriptional regulators within the chromatin environment. Trends Genet. 2011;27:465–474. doi: 10.1016/j.tig.2011.07.002. PubMed DOI

Clark K.L., Halay E.D., Lai E., Burley S.K. Co-crystal structure of the HNF-3/fork head DNA-recognition motif resembles histone H5. Nature. 1993;364:412–420. doi: 10.1038/364412a0. PubMed DOI

LaRonde-LeBlanc N.A., Wolberger C. Structure of Hoxa9 and Pbx1 bound to DNA: Hox hexapeptide and DNA recognition anterior to posterior. Genes Dev. 2003;17:2060–2072. doi: 10.1101/gad.1103303. PubMed DOI PMC

Chen Y., Zhang X., Dantas Machado A.C., Ding Y., Chen Z., Qin P.Z., Rohs R., Chen L. Structure of p53 binding to the bax response element reveals DNA unwinding and compression to accommodate base-pair insertion. Nucleic Acids Res. 2013;41:8368–8376. doi: 10.1093/nar/gkt584. PubMed DOI PMC

Frouws T.D., Duda S.C., Richmond T.J. X-ray structure of the MMTV-A nucleosome core. Proc. Natl. Acad. Sci. USA. 2016;113:1214–1219. doi: 10.1073/pnas.1524607113. PubMed DOI PMC

Osakabe A., Adachi F., Arimura Y., Maehara K., Ohkawa Y., Kurumizaka H. Influence of DNA methylation on positioning and DNA flexibility of nucleosomes with pericentric satellite DNA. Open Biol. 2015;5 doi: 10.1098/rsob.150128. PubMed DOI PMC

Emamzadah S., Tropia L., Vincenti I., Falquet B., Halazonetis T.D. Reversal of the DNA-binding-induced loop L1 conformational switch in an engineered human p53 protein. J. Mol. Biol. 2014;426:936–944. doi: 10.1016/j.jmb.2013.12.020. PubMed DOI

Rhee S., Martin R.G., Rosner J.L., Davies D.R. A novel DNA-binding motif in MarA: The first structure for an AraC family transcriptional activator. Proc. Natl. Acad. Sci. USA. 1998;95:10413–10418. doi: 10.1073/pnas.95.18.10413. PubMed DOI PMC

Ngo H.B., Kaiser J.T., Chan D.C. The mitochondrial transcription and packaging factor tfam imposes a U-turn on mitochondrial DNA. Nat. Struct. Mol. Biol. 2011;18:1290–1296. doi: 10.1038/nsmb.2159. PubMed DOI PMC

Jain D., Kim Y., Maxwell K.L., Beasley S., Zhang R., Gussin G.N., Edwards A.M., Darst S.A. Crystal structure of bacteriophage λcII and its DNA complex. Mol. Cell. 2005;19:259–269. doi: 10.1016/j.molcel.2005.06.006. PubMed DOI

Ngo H.B., Lovely G.A., Phillips R., Chan D.C. Distinct structural features of tfam drive mitochondrial DNA packaging versus transcriptional activation. Nat. Commun. 2014;5:3077. doi: 10.1038/ncomms4077. PubMed DOI PMC

Zhang R.G., Pappas K.M., Brace J.L., Miller P.C., Oulmassov T., Molyneaux J.M., Anderson J.C., Bashkin J.K., Winans S.C., Joachimiak A. Structure of a bacterial quorum-sensing transcription factor complexed with pheromone and DNA. Nature. 2002;417:971–974. doi: 10.1038/nature00833. PubMed DOI

Albright R.A., Matthews B.W. Crystal structure of lambda-Cro bound to a consensus operator at 3.0 a resolution. J. Mol. Biol. 1998;280:137–151. doi: 10.1006/jmbi.1998.1848. PubMed DOI

Adams P.D., Afonine P.V., Bunkóczi G., Chen V.B., Davis I.W., Echols N., Headd J.J., Hung L.-W., Kapral G.J., Grosse-Kunstleve R.W., et al. Phenix: A comprehensive python-based system for macromolecular structure solution. Acta Crystallogr. D. 2010;66:213–221. doi: 10.1107/S0907444909052925. PubMed DOI PMC

Murshudov G.N., Vagin A.A., Dodson E.J. Refinement of macromolecular structures by the maximum-likelihood method. Acta Crystallogr. D. 1997;53:240–255. doi: 10.1107/S0907444996012255. PubMed DOI

Tickle I.J. Statistical quality indicators for electron-density maps. Acta Crystallogr. D. 2012;68:454–467. doi: 10.1107/S0907444911035918. PubMed DOI PMC

Branden C., Jones T. Between objectivity and subjectivity. Nature. 1990;343:687–689. doi: 10.1038/343687a0. DOI

Kleywegt G.J., Harris M.R., Zou J.-Y., Taylor T.C., Wahlby A., Jones T.A. The uppsala electron-density server. Acta Crystallogr. D. 2004;60:2240–2249. doi: 10.1107/S0907444904013253. PubMed DOI

Virstedt J., Berge T., Henderson R.M., Waring M.J., Travers A.A. The influence of DNA stiffness upon nucleosome formation. J. Struct. Biol. 2004;148:66–85. doi: 10.1016/j.jsb.2004.03.007. PubMed DOI

Zhang Y., Xi Z., Hegde R.S., Shakked Z., Crothers D.M. Predicting indirect readout effects in protein–DNA interactions. Proc. Natl. Acad. Sci. USA. 2004;101:8337–8341. doi: 10.1073/pnas.0402319101. PubMed DOI PMC

Lowary P.T., Widom J. New DNA sequence rules for high affinity binding to histone octamer and sequence-directed nucleosome positioning. J. Mol. Biol. 1998;276:19–42. doi: 10.1006/jmbi.1997.1494. PubMed DOI

Zhou X., Blocker A.W., Airoldi E.M., O’Shea E.K. A computational approach to map nucleosome positions and alternative chromatin states with base pair resolution. eLife. 2016;5:e16970. doi: 10.7554/eLife.16970. PubMed DOI PMC

Satchwell S.C., Drew H.R., Travers A.A. Sequence periodicities in chicken nucleosome core DNA. J. Mol. Biol. 1986;191:659–675. doi: 10.1016/0022-2836(86)90452-3. PubMed DOI

Segal E., Fondufe-Mittendorf Y., Chen L., Thastrom A., Field Y., Moore I.K., Wang J.P., Widom J. A genomic code for nucleosome positioning. Nature. 2006;442:772–778. doi: 10.1038/nature04979. PubMed DOI PMC

Trifonov E.N., Nibhani R. Review fifteen years of search for strong nucleosomes. Biopolymers. 2015;103:432–437. doi: 10.1002/bip.22604. PubMed DOI

Ong M.S., Richmond T.J., Davey C.A. DNA stretching and extreme kinking in the nucleosome core. J. Mol. Biol. 2007;368:1067–1074. doi: 10.1016/j.jmb.2007.02.062. PubMed DOI

Chua E.Y., Vasudevan D., Davey G.E., Wu B., Davey C.A. The mechanics behind DNA sequence-dependent properties of the nucleosome. Nucleic Acids Res. 2012;40:6338–6352. doi: 10.1093/nar/gks261. PubMed DOI PMC

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