Abstract
Nucleosome positioning plays an essential role in various fundamental cellular processes by modulating the accessibility of DNA to binding proteins. Understanding the mechanisms and precise recognition of nucleosome positioning along genomic sequences are substantially important for elucidating regulations of cellular processes such as DNA replication, recombination, and gene transcription. In this report, we present a knowledge-based model for calculation of deformational energy of nucleosomal DNA and apply the model to the prediction of nucleosome positioning along the genome of Saccharomyces cerevisiae accurately. The model successfully predicted genome-wide in vitro nucleosome positions. When combined with quadratic discriminant classifier, the model achieved an accuracy of 92.9 % in discriminating in vitro nucleosome forming sequences from nucleosome inhibiting sequences. Our result supports the debated notion that the nucleosome positioning in the genomic sequences is guided primarily by deformational properties of DNA.
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Abbreviations
- MNase:
-
Micrococcal nuclease
- NDRs:
-
Nucleosome-depleted regions
- TSS:
-
Transcription start sites
- TES:
-
Transcription end sites
- ARS:
-
Autonomously replicating sequence
- ACS:
-
ARS consensus sequences
- ID:
-
Increment of diversity
- QD:
-
Quadratic determinant
- ORC:
-
Origin recognition complex
References
Albert I, Mavrich TN, Tomsho LP et al (2007) Translational and rotational settings of H2A.Z nucleosomes across the Saccharomyces cerevisiae genome. Nature 446:572–576
Bao Y, White CL, Luger K (2006) Nucleosome core particles containing a poly(dA.dT) sequence element exhibit a locally distorted DNA structure. J Mol Biol 361:617–624
Barski A, Cuddapah S, Cui K et al (2007) High-resolution profiling of histone methylations in the human genome. Cell 129:823–837
Battistini F, Hunter CA, Gardiner EJ, Packer MJ (2010) Structural mechanics of DNA wrapping in the nucleosome. J Mol Biol 396:264–279
Berbenetz NM, Nislow C, Brown GW (2010) Diversity of eukaryotic DNA replication origins revealed by genome-wide analysis of chromatin structure. PLoS Genet 6
Cherry JM, Adler C, Ball C et al (1998) SGD: Saccharomyces Genome Database. Nucleic Acids Res 26:73–79
Dickerson RE (1989) Definitions and nomenclature of nucleic acid structure parameters. J Biomol Struct Dyn 6:627–634
Drew HR, Travers AA (1985) DNA bending and its relation to nucleosome positioning. J Mol Biol 186:773–790
Eaton ML, Galani K, Kang S, Bell SP, MacAlpine DM (2010) Conserved nucleosome positioning defines replication origins. Genes Dev 24:748–753
Field Y, Kaplan N, Fondufe-Mittendorf Y et al (2008) Distinct modes of regulation by chromatin encoded through nucleosome positioning signals. PLoS Comput Biol 4:e1000216
Flaus A, Luger K, Tan S, Richmond TJ (1996) Mapping nucleosome position at single base-pair resolution by using site-directed hydroxyl radicals. Proc Natl Acad Sci U S A 93:1370–1375
Gabdank I, Barash D, Trifonov EN (2010) Single-base resolution nucleosome mapping on DNA sequences. J Biomol Struct Dyn 28:107–122
Jenuwein T, Allis CD (2001) Translating the histone code. Science 293:1074–1080
Kaplan N, Moore IK, Fondufe-Mittendorf Y et al (2009) The DNA-encoded nucleosome organization of a eukaryotic genome. Nature 458:362–366
Kornberg RD, Lorch Y (1999) Twenty-five years of the nucleosome, fundamental particle of the eukaryote chromosome. Cell 98:285–294
Laxton RR (1978) The measure of diversity. J Theor Biol 70:51–67
Lee W, Tillo D, Bray N et al (2007) A high-resolution atlas of nucleosome occupancy in yeast. Nat Genet 39:1235–1244
Li QZ, Lu ZQ (2001) The prediction of the structural class of protein: application of the measure of diversity. J Theor Biol 213:493–502
Lu J, Luo L, Zhang L, Chen W, Zhang Y (2010) Increment of diversity with quadratic discriminant analysis—an efficient tool for sequence pattern recognition in bioinformatics. Open Access Bioinf 2:89–96
Mavrich TN, Ioshikhes IP, Venters BJ et al (2008a) A barrier nucleosome model for statistical positioning of nucleosomes throughout the yeast genome. Genome Res 18:1073–1083
Mavrich TN, Jiang C, Ioshikhes IP et al (2008b) Nucleosome organization in the Drosophila genome. Nature 453:358–362
Miele V, Vaillant C, Daubenton-Carafa Y, Thermes C, Grange T (2008) DNA physical properties determine nucleosome occupancy from yeast to fly. Nucleic Acids Res 36:3746–3756
Morozov AV, Fortney K, Gaykalova DA, Studitsky VM, Widom J, Siggia ED (2009) Using DNA mechanics to predict in vitro nucleosome positions and formation energies. Nucleic Acids Res 37:4707–4722
Olson WK, Gorin AA, Lu XJ, Hock LM, Zhurkin VB (1998) DNA sequence-dependent deformability deduced from protein–DNA crystal complexes. Proc Natl Acad Sci U S A 95:11163–11168
Peckham HE, Thurman RE, Fu Y et al (2007) Nucleosome positioning signals in genomic DNA. Genome Res 17:1170–1177
Rapoport AE, Frenkel ZM, Trifonov EN (2011) Nucleosome positioning pattern derived from oligonucleotide compositions of genomic sequences. J Biomol Struct Dyn 28:567–574
Richmond TJ, Davey CA (2003) The structure of DNA in the nucleosome core. Nature 423:145–150
Richmond TJ, Finch JT, Rushton B, Rhodes D, Klug A (1984) Structure of the nucleosome core particle at 7 A resolution. Nature 311:532–537
Satchwell SC, Drew HR, Travers AA (1986) Sequence periodicities in chicken nucleosome core DNA. J Mol Biol 191:659–675
Schones DE, Cui K, Cuddapah S et al (2008) Dynamic regulation of nucleosome positioning in the human genome. Cell 132:887–898
Schwab DJ, Bruinsma RF, Rudnick J, Widom J (2008) Nucleosome switches. Phys Rev Lett 100:228105
Scipioni A, Morosetti S, De Santis P (2009) A statistical thermodynamic approach for predicting the sequence-dependent nucleosome positioning along genomes. Biopolymers 91:1143–1153
Segal E, Fondufe-Mittendorf Y, Chen L et al (2006) A genomic code for nucleosome positioning. Nature 442:772–778
Segal E, Widom J (2009) Poly(dA:dT) tracts: major determinants of nucleosome organization. Curr Opin Struct Biol 19:65–71
Tolkunov D, Morozov AV (2010) Genomic studies and computational predictions of nucleosome positions and formation energies. Adv Protein Chem Struct Biol 79:1–57
Wyrick JJ, Holstege FC, Jennings EG et al (1999) Chromosomal landscape of nucleosome-dependent gene expression and silencing in yeast. Nature 402:418–421
Xing Y, Zhao X, Cai L (2011) Prediction of nucleosome occupancy in Saccharomyces cerevisiae using position-correlation scoring function. Genomics 98:359–366
Xu F, Olson WK (2010) DNA architecture, deformability, and nucleosome positioning. J Biomol Struct Dyn 27:725–739
Yuan GC, Liu YJ, Dion MF et al (2005) Genome-scale identification of nucleosome positions in S. cerevisiae. Science 309:626–630
Zhang L, Luo L (2003) Splice site prediction with quadratic discriminant analysis using diversity measure. Nucleic Acids Res 31:6214–6220
Zhang MQ (1997) Identification of protein coding regions in the human genome by quadratic discriminant analysis. Proc Natl Acad Sci U S A 94:565–568
Zhang Y, Moqtaderi Z, Rattner BP et al (2009) Intrinsic histone–DNA interactions are not the major determinant of nucleosome positions in vivo. Nat Struct Mol Biol 16:847–852
Zhang Y, Moqtaderi Z, Rattner BP et al (2010) Evidence against a genomic code for nucleosome positioning. Reply to "Nucleosome sequence preferences influence in vivo nucleosome organization". Nat Struct Mol Biol 17:920–923
Zhao X, Pei Z, Liu J, Qin S, Cai L (2010) Prediction of nucleosome DNA formation potential and nucleosome positioning using increment of diversity combined with quadratic discriminant analysis. Chromosome Res 18:777–785
Acknowledgments
We thank Yong-Qiang Xing for his helpful discussions. This work was supported by grants from the National Natural Science Foundation (61102162), Inner Mongolia Natural Science Foundation (2010MS0510), the Research Program of Higher Education of Inner Mongolia Autonomous Region (NJ10098), and the Innovation Fund of Inner Mongolia University of Science and Technology (2009NC005).
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Responsible Editor: Dean A. Jackson.
This work was supported by grants from the National Natural Science Foundation (61102162) Inner Mongolia Natural Science Foundation (2010MS0510), the Research Program of Higher Education of Inner Mongolia Autonomous Region (NJ10098), and the Innovation Fund of Inner Mongolia University of Science and Technology (2009NC005).
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Wang, JY., Wang, J. & Liu, G. Calculation of nucleosomal DNA deformation energy: its implication for nucleosome positioning. Chromosome Res 20, 889–902 (2012). https://doi.org/10.1007/s10577-012-9328-6
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DOI: https://doi.org/10.1007/s10577-012-9328-6