About this Journal Submit a Manuscript Table of Contents
ISRN Molecular Biology
Volume 2012 (2012), Article ID 245706, 5 pages
http://dx.doi.org/10.5402/2012/245706
Review Article

Nucleosome Positioning

Agricultural Bioinformatics Research Unit, Graduate School of Agricultural and Life Sciences, University of Tokyo, Tokyo 113-8657, Japan

Received 19 August 2012; Accepted 17 September 2012

Academic Editors: Y.-K. Jang and A. J. Molenaar

Copyright © 2012 Hiromi Nishida. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Nucleosome positioning is not only related to genomic DNA compaction but also to other biological functions. After the chromatin is digested by micrococcal nuclease, nucleosomal (nucleosome-bound) DNA fragments can be sequenced and mapped on the genomic DNA sequence. Due to the development of modern DNA sequencing technology, genome-wide nucleosome mapping has been performed in a wide range of eukaryotic species. Comparative analyses of the nucleosome positions have revealed that the nucleosome is more frequently formed in exonic than intronic regions, and that most of transcription start and translation (or transcription) end sites are located in nucleosome linker DNA regions, indicating that nucleosome positioning influences transcription initiation, transcription termination, and gene splicing. In addition, nucleosomal DNA contains guanine and cytosine (G + C)-rich sequences and a high level of cytosine methylation. Thus, the nucleosome positioning system has been conserved during eukaryotic evolution.

1. Introduction

Eukaryotic genomic DNA is packaged with histone proteins to form chromatin [1, 2]. The most fundamental repeating unit of chromatin is the nucleosome, which consists of an octamer of histones (2 copies of each histone protein: H2A, H2B, H3, and H4) and the genomic DNA wrapped around the octamer [3, 4]. Modification (e.g., acetylation, methylation, and phosphorylation) of the nucleosomal core histones influences chromatin structure and biological functions [57]. The modified nucleosome should be formed at the genomic position or in the genomic region. In this paper, I will focus on nucleosome positioning (not histone modification), because nucleosome positioning is not only related to compacting the genomic DNA but also to gene regulation [817].

Due to the development of DNA sequencing technology and genomic tiling array technology, genome-wide nucleosome mapping has been performed in a wide range of eukaryotic species, including the budding ascomycetous yeast, Saccharomyces cerevisiae [19]; the nematode, Caenorhabditis elegans [20]; the fruit fly, Drosophila melanogaster [21]; humans, Homo sapiens [22]; the malaria parasite, Plasmodium falciparum [23]; the filamentous ascomycete, Aspergillus fumigatus [24]; the fission ascomycetous yeast, Schizosaccharomyces pombe [25]; the plant, Arabidopsis thaliana [26]; several ascomycetous yeasts [27]; the mouse, Mus musculus [28]; the basidiomycete, Mixia osmundae [29]; the amoebozoa, Dictyostelium discoideum [30].

2. Nucleosome Positioning and DNA Sequence Preference

The DNA sequence plays an important role in nucleosome positioning [3137]. Genome-wide analyses of nucleosome positioning have revealed that DNA sequence preference exists for nucleosome occupancy [29, 38, 39]. The nucleosome occupancy reflects average nucleosome positioning levels on a given region of DNA in a population of cells [4043]. For example, the dinucleotide sequences AA and TT are depleted in nucleosome-forming regions in different organisms [29, 39, 44], whereas the G + C content is highly correlated with nucleosome occupancy [45, 46]. In addition, it has been reported that nucleosomal DNA cytosines are more highly methylated than nucleosome linker DNA cytosines in humans and the plant Arabidopsis [26]. These results suggest that DNA sequence preference in nucleosome occupancy has been conserved during eukaryotic evolution.

Genome-wide nucleosome positioning data suggest that nucleosome occupancy restricts the range of genomic G + C content. Bacteria and Archaea, which lack nucleosomes, have a wide range of G + C content. In contrast, the genomic G + C content distribution of Eukarya is completely different from that of Bacteria and Archaea (Figure 1). This distribution difference may be related to the differences in the conservation level of histones and nucleoid-associated proteins; although histone proteins are highly conserved between different organisms, nucleoid-associated proteins vary among Bacteria and Archaea [4750].

fig1
Figure 1: Distribution of the genomic G + C content of Bacteria, Archaea, and Eukarya. The G + C content data were obtained from the Genome Composition Database [18].

3. Nucleosome Positioning around the Transcription Start Site

Nucleosome depletion in the vicinity of the transcription start site (TSS) has been indicated [5153]. Indeed, nucleosome-free regions are pervasive in the gene promoters of yeast [26, 54, 55]. Moreover, the nucleosome organization around TSSs is very similar among different organisms [20, 29, 30, 39, 54, 55]. The nucleosome position profile is sharper in the downstream region of the TSS. Nucleosomes downstream from the nucleosome-free region are well positioned, with positioning decaying with increasing distance into the protein-coding region. Nucleosome positioning is more conserved in gene promoters than in gene bodies, suggesting that nucleosome positioning in the gene promoter plays an important role in gene transcription [19, 27, 52, 56, 57].

On the other hand, nucleosome positioning in vivo differs from that in vitro, indicating that systems other than DNA sequence preference are involved in nucleosome positioning [40, 41, 58]. Recently, it was reported that the most conserved nucleosome position (the +1 nucleosome), which is the sharpest in the nucleosome position profile, is maintained by ATP-dependent factors in S. cerevisiae [59, 60]. It remains uncertain whether nucleosome positioning in the gene promoter has been evolutionarily conserved as a major driving force in gene expression [15, 27, 36] or not [57, 61, 62].

4. Nucleosome Positioning around the Translation (or Transcription) End Site

Genome-wide nucleosome mapping analyses of the ascomycete S. cerevisiae revealed that nucleosome depletion is also found around translation end sites as well as TSSs [63, 64]. In the basidiomycete M. osmundae, dinucleosome—but not mononucleosome—depletion is clearly found around TSSs and translation end sites [29]. These results suggest that the nucleosome linker DNA length of M. osmundae around TSSs and translation end sites is shorter than that of S. cerevisiae. Nucleosome depletion around transcription end sites is also found in Drosophila and Dictyostelium [21, 30]. The regions around both transcription start and end sites have DNA sequences rich in adenine and thymine, which disfavor core histones [21, 30, 54]. Recently, some chromatin remodelers have been reported to locate around transcription start and end sites in S. cerevisiae [65].

5. Nucleosome Positioning in Exonic and Intronic Regions

Chromatin structure may be linked to gene splicing [66, 67]. Genome-wide nucleosome mapping analyses have shown that the nucleosome occupancy level in exons is higher than that in introns [6872]. DNA sequence differences between exons and introns are correlated with nucleosomal DNA preferences [73], as exon DNA sequences have a higher G + C content than intron DNA sequences [70]. As described above, nucleosomal DNA prefers (G + C)-rich sequences.

6. Conclusions

Although the nucleosome positioning system differs between the ascomycetous budding yeast S. cerevisiae and the ascomycetous fission yeast Sch. pombe [25], genome-wide comparative analyses of nucleosome positions have revealed that nucleosome positioning shares a common feature among different organisms. Nucleosomal DNA has a higher G + C content and a higher level of cytosine methylation than nucleosome linker DNA (Figure 2). In addition, nucleosome positioning is found more frequently in exonic than in intronic regions. Transcription start sites and translation (or transcription) end sites are more frequently located in nucleosome linker DNA than in nucleosomal DNA. Thus, not only the structures of core histone proteins but also the nucleosome positioning systems have been greatly conserved during eukaryotic evolution.

245706.fig.002
Figure 2: Difference between nucleosome-forming and linker regions.

References

  1. R. D. Kornberg, “Structure of chromatin,” Annual Review of Biochemistry, vol. 46, pp. 931–954, 1977. View at Scopus
  2. T. Igo-Kemenes, W. Hörz, and H. G. Zachau, “Chromatin,” Annual Review of Biochemistry, vol. 51, pp. 89–121, 1982. View at Scopus
  3. K. Luger, A. W. Mäder, R. K. Richmond, D. F. Sargent, and T. J. Richmond, “Crystal structure of the nucleosome core particle at 2.8 Å resolution,” Nature, vol. 389, no. 6648, pp. 251–260, 1997. View at Publisher · View at Google Scholar · View at Scopus
  4. T. J. Richmond and C. A. Davey, “The structure of DNA in the nucleosome core,” Nature, vol. 423, no. 6936, pp. 145–150, 2003. View at Publisher · View at Google Scholar · View at Scopus
  5. B. D. Strahl and C. D. Allis, “The language of covalent histone modifications,” Nature, vol. 403, no. 6765, pp. 41–45, 2000. View at Publisher · View at Google Scholar · View at Scopus
  6. T. Jenuwein and C. D. Allis, “Translating the histone code,” Science, vol. 293, no. 5532, pp. 1074–1080, 2001. View at Publisher · View at Google Scholar · View at Scopus
  7. J. C. Rice and C. D. Allis, “Histone methylation versus histone acetylation: new insights into epigenetic regulation,” Current Opinion in Cell Biology, vol. 13, no. 3, pp. 263–273, 2001. View at Publisher · View at Google Scholar · View at Scopus
  8. M. Han and M. Grunstein, “Nucleosome loss activates yeast downstream promoters in vivo,” Cell, vol. 55, no. 6, pp. 1137–1145, 1988. View at Scopus
  9. M. Grunstein, “Histone function in transcription,” Annual Review of Cell Biology, vol. 6, pp. 643–678, 1990. View at Scopus
  10. Q. Lu, L. L. Wallrath, and S. C. R. Elgin, “Nucleosome positioning and gene regulation,” Journal of Cellular Biochemistry, vol. 55, no. 1, pp. 83–92, 1994. View at Publisher · View at Google Scholar · View at Scopus
  11. P. D. Gregory and W. Hörz, “Life with nucleosomes: chromatin remodelling in gene regulation,” Current Opinion in Cell Biology, vol. 10, no. 3, pp. 339–345, 1998. View at Publisher · View at Google Scholar · View at Scopus
  12. J. J. Wyrick, F. C. P. Holstege, E. G. Jennings et al., “Chromosomal landscape of nucleosome-dependent gene expression and silencing in yeast,” Nature, vol. 402, no. 6760, pp. 418–421, 1999. View at Publisher · View at Google Scholar · View at Scopus
  13. O. J. Rando and K. Ahmad, “Rules and regulation in the primary structure of chromatin,” Current Opinion in Cell Biology, vol. 19, no. 3, pp. 250–256, 2007. View at Publisher · View at Google Scholar · View at Scopus
  14. I. Tirosh and N. Barkai, “Two strategies for gene regulation by promoter nucleosomes,” Genome Research, vol. 18, no. 7, pp. 1084–1091, 2008. View at Publisher · View at Google Scholar · View at Scopus
  15. Y. Field, Y. Fondufe-Mittendorf, I. K. Moore et al., “Gene expression divergence in yeast is coupled to evolution of DNA-encoded nucleosome organization,” Nature Genetics, vol. 41, no. 4, pp. 438–445, 2009. View at Publisher · View at Google Scholar · View at Scopus
  16. C. Jiang and B. F. Pugh, “Nucleosome positioning and gene regulation: advances through genomics,” Nature Reviews Genetics, vol. 10, no. 3, pp. 161–172, 2009. View at Publisher · View at Google Scholar · View at Scopus
  17. L. Bai and A. V. Morozov, “Gene regulation by nucleosome positioning,” Trends in Genetics, vol. 26, no. 11, pp. 476–483, 2010. View at Publisher · View at Google Scholar · View at Scopus
  18. K. Kryukov, K. Sumiyama, K. Ikeo, T. Gojobori, and N. Saitou, “A new database (GCD) on genome composition for eukaryote and prokaryote genome sequences and their initial analyses,” Genome Biology and Evolution, vol. 4, no. 4, pp. 501–512, 2012. View at Publisher · View at Google Scholar
  19. G.-C. Yuan, Y.-J. Liu, M. F. Dion et al., “Molecular biology: genome-scale identification of nucleosome positions in S. cerevisiae,” Science, vol. 309, no. 5734, pp. 626–630, 2005. View at Publisher · View at Google Scholar · View at Scopus
  20. A. Valouev, J. Ichikawa, T. Tonthat et al., “A high-resolution, nucleosome position map of C. elegans reveals a lack of universal sequence-dictated positioning,” Genome Research, vol. 18, no. 7, pp. 1051–1063, 2008. View at Publisher · View at Google Scholar · View at Scopus
  21. T. N. Mavrich, C. Jiang, I. P. Ioshikhes et al., “Nucleosome organization in the Drosophila genome,” Nature, vol. 453, no. 7193, pp. 358–362, 2008. View at Publisher · View at Google Scholar · View at Scopus
  22. D. E. Schones, K. Cui, S. Cuddapah et al., “Dynamic regulation of nucleosome positioning in the human genome,” Cell, vol. 132, no. 5, pp. 887–898, 2008. View at Publisher · View at Google Scholar · View at Scopus
  23. S. J. Westenberger, L. Cui, N. Dharia, E. Winzeler, and L. Cui, “Genome-wide nucleosome mapping of Plasmodium falciparum reveals histone-rich coding and histone-poor intergenic regions and chromatin remodeling of core and subtelomeric genes,” BMC Genomics, vol. 10, article 610, 2009. View at Publisher · View at Google Scholar · View at Scopus
  24. H. Nishida, T. Motoyama, S. Yamamoto, H. Aburatani, and H. Osada, “Genome-wide maps of mono- and di-nucleosomes of Aspergillus fumigatus,” Bioinformatics, vol. 25, no. 18, pp. 2295–2297, 2009. View at Publisher · View at Google Scholar · View at Scopus
  25. A. B. Lantermann, T. Straub, A. Strålfors, G.-C. Yuan, K. Ekwall, and P. Korber, “Schizosaccharomyces pombe genome-wide nucleosome mapping reveals positioning mechanisms distinct from those of Saccharomyces cerevisiae,” Nature Structural and Molecular Biology, vol. 17, no. 2, pp. 251–257, 2010. View at Publisher · View at Google Scholar · View at Scopus
  26. R. K. Chodavarapu, S. Feng, Y. V. Bernatavichute et al., “Relationship between nucleosome positioning and DNA methylation,” Nature, vol. 466, no. 7304, pp. 388–392, 2010. View at Publisher · View at Google Scholar · View at Scopus
  27. A. M. Tsankov, D. A. Thompson, A. Socha, A. Regev, and O. J. Rando, “The role of nucleosome positioning in the evolution of gene regulation,” PLoS Biology, vol. 8, no. 7, Article ID e1000414, 2010. View at Publisher · View at Google Scholar · View at Scopus
  28. Z. Li, J. Schug, G. Tuteja, P. White, and K. H. Kaestner, “The nucleosome map of the mammalian liver,” Nature Structural and Molecular Biology, vol. 18, no. 6, pp. 742–746, 2011. View at Publisher · View at Google Scholar · View at Scopus
  29. H. Nishida, S. Kondo, T. Matsumoto et al., “Characteristics of nucleosomes and linker DNA regions on the genome of the basidiomycete Mixia osmundae revealed by mono- and dinucleosome mapping,” Open Biology, vol. 2, Article ID 120043, 2012.
  30. G. S. Chang, A. A. Noegel, T. N. Mavrich et al., “Unusual combinatorial involvement of poly-A/T tracts in organizing genes and chromatin in Dictyostelium,” Genome Research, vol. 22, no. 6, pp. 1098–1106, 2012. View at Publisher · View at Google Scholar
  31. H. R. Drew and A. A. Travers, “DNA bending and its relation to nucleosome positioning,” Journal of Molecular Biology, vol. 186, no. 4, pp. 773–790, 1985. View at Scopus
  32. S. C. Satchwell, H. R. Drew, and A. A. Travers, “Sequence periodicities in chicken nucleosome core DNA,” Journal of Molecular Biology, vol. 191, no. 4, pp. 659–675, 1986. View at Scopus
  33. P. T. Lowary and J. Widom, “New DNA sequence rules for high affinity binding to histone octamer and sequence-directed nucleosome positioning,” Journal of Molecular Biology, vol. 276, no. 1, pp. 19–42, 1998. View at Publisher · View at Google Scholar · View at Scopus
  34. E. Segal, Y. Fondufe-Mittendorf, L. Chen et al., “A genomic code for nucleosome positioning,” Nature, vol. 442, no. 7104, pp. 772–778, 2006. View at Publisher · View at Google Scholar · View at Scopus
  35. H. E. Peckham, R. E. Thurman, Y. Fu et al., “Nucleosome positioning signals in genomic DNA,” Genome Research, vol. 17, no. 8, pp. 1170–1177, 2007. View at Publisher · View at Google Scholar · View at Scopus
  36. N. Kaplan, T. R. Hughes, J. D. Lieb, J. Widom, and E. Segal, “Contribution of histone sequence preferences to nucleosome organization: proposed definitions and methodology,” Genome Biology, vol. 11, no. 11, article 140, 2010. View at Publisher · View at Google Scholar · View at Scopus
  37. I. Ioshikhes, S. Hosid, and B. F. Pugh, “Variety of genomic DNA patterns for nucleosome positioning,” Genome Research, vol. 21, no. 11, pp. 1863–11871, 2011. View at Publisher · View at Google Scholar
  38. A. Tsankov, Y. Yanagisawa, N. Rhind, A. Regev, and O. J. Rando, “Evolutionary divergence of intrinsic and trans-regulated nucleosome positioning sequences reveals plastic rules for chromatin organization,” Genome Research, vol. 21, no. 11, pp. 1851–1862, 2011. View at Publisher · View at Google Scholar
  39. A. Valouev, S. M. Johnson, S. D. Boyd, C. L. Smith, A. Z. Fire, and A. Sidow, “Determinants of nucleosome organization in primary human cells,” Nature, vol. 474, no. 7352, pp. 516–520, 2011. View at Publisher · View at Google Scholar · View at Scopus
  40. A. Stein, T. E. Takasuka, and C. K. Collings, “Are nucleosome positions in vivo primarily determined by histone-DNA sequence preferences?” Nucleic Acids Research, vol. 38, no. 3, pp. 709–719, 2010. View at Publisher · View at Google Scholar · View at Scopus
  41. Y. Zhang, Z. Moqtaderi, B. P. Rattner et al., “Intrinsic histone-DNA interactions are not the major determinant of nucleosome positions in vivo,” Nature Structural and Molecular Biology, vol. 16, no. 8, pp. 847–852, 2009. View at Publisher · View at Google Scholar · View at Scopus
  42. N. Kaplan, I. Moore, Y. Fondufe-Mittendorf et al., “Nucleosome sequence preferences influence in vivo nucleosome organization,” Nature Structural and Molecular Biology, vol. 17, no. 8, pp. 918–920, 2010. View at Publisher · View at Google Scholar · View at Scopus
  43. B. F. Pugh, “A preoccupied position on nucleosomes,” Nature Structural and Molecular Biology, vol. 17, no. 8, p. 923, 2010. View at Publisher · View at Google Scholar · View at Scopus
  44. S. M. Johnson, F. J. Tan, H. L. McCullough, D. P. Riordan, and A. Z. Fire, “Flexibility and constraint in the nucleosome core landscape of Caenorhabditis elegans chromatin,” Genome Research, vol. 16, no. 12, pp. 1505–1516, 2006. View at Publisher · View at Google Scholar · View at Scopus
  45. W. Lee, D. Tillo, N. Bray et al., “A high-resolution atlas of nucleosome occupancy in yeast,” Nature Genetics, vol. 39, no. 10, pp. 1235–1244, 2007. View at Publisher · View at Google Scholar · View at Scopus
  46. D. Tillo and T. R. Hughes, “G+C content dominates intrinsic nucleosome occupancy,” BMC Bioinformatics, vol. 10, article 442, 2009. View at Publisher · View at Google Scholar · View at Scopus
  47. S. Rimsky and A. Travers, “Pervasive regulation of nucleoid structure and function by nucleoid-associated proteins,” Current Opinion in Microbiology, vol. 14, no. 2, pp. 136–141, 2011. View at Publisher · View at Google Scholar · View at Scopus
  48. T. Takeda, C.-S. Yun, M. Shintani, H. Yamane, and H. Nojiri, “Distribution of genes encoding nucleoid-associated protein homologs in plasmids,” International Journal of Evolutionary Biology, vol. 2011, Article ID 685015, 2011.
  49. S. S. Ali, B. Xia, J. Liu, and W. W. Nararre, “Silencing of foreign DNA in bacteria,” Current Opinion in Microbiology, vol. 15, no. 2, pp. 175–181, 2012.
  50. H. Nishida, “Genome DNA sequence variation, evolution, and function in bacteria and archaea,” Current Issues in Molecular Biology, vol. 15, no. 1, pp. 19–24, 2013.
  51. B. E. Bernstein, C. L. Liu, E. L. Humphrey, E. O. Perlstein, and S. L. Schreiber, “Global nucleosome occupancy in yeast,” Genome Biology, vol. 5, no. 9, Article ID R62, 2004. View at Scopus
  52. C.-K. Lee, Y. Shibata, B. Rao, B. D. Strahl, and J. D. Lieb, “Evidence for nucleosome depletion at active regulatory regions genome-wide,” Nature Genetics, vol. 36, no. 8, pp. 900–905, 2004. View at Publisher · View at Google Scholar · View at Scopus
  53. H. Nishida, T. Suzuki, S. Kondo, H. Miura, Y. I. Fujimura, and Y. Hayashizaki, “Histone H3 acetylated at lysine 9 in promoter is associated with low nucleosome density in the vicinity of transcription start site in human cell,” Chromosome Research, vol. 14, no. 2, pp. 203–211, 2006. View at Publisher · View at Google Scholar · View at Scopus
  54. T. N. Mavrich, I. P. Ioshikhes, B. J. Venters et al., “A barrier nucleosome model for statistical positioning of nucleosomes throughout the yeast genome,” Genome Research, vol. 18, no. 7, pp. 1073–1083, 2008. View at Publisher · View at Google Scholar · View at Scopus
  55. S. Shivaswamy, A. Bhinge, Y. Zhao, S. Jones, M. Hirst, and V. R. Iyer, “Dynamic remodeling of individual nucleosomes across a eukaryotic genome in response to transcriptional perturbation,” PLoS Biology, vol. 6, no. 3, Article ID e65, 2008. View at Publisher · View at Google Scholar · View at Scopus
  56. H. Nishida, T. Motoyama, Y. Suzuki, S. Yamamoto, H. Aburatani, and H. Osada, “Genome-wide maps of mononucleosomes and dinucleosomes containing hyperacetylated histones of Aspergillus fumigatus,” PloS ONE, vol. 5, no. 3, Article ID e9916, 2010. View at Scopus
  57. H. Nishida, “Conservation of nucleosome positions in duplicated and orthologous gene pairs,” The Scientific World Journal, vol. 2012, Article ID 298174, 2012.
  58. A. Hughes and O. J. Rando, “Chromatin “programming” by sequence-is there more to the nucleosome code than %GC?” Journal of Biology, vol. 8, no. 11, article 96, 2009. View at Publisher · View at Google Scholar · View at Scopus
  59. T. Gkikopoulos, P. Schofield, V. Singh et al., “A role for Snf2-related nucleosome-spacing enzymes in genome-wide nucleosome organization,” Science, vol. 333, no. 6050, pp. 1758–1760, 2011. View at Publisher · View at Google Scholar
  60. Z. Zhang, C. J. Wippo, M. Wal, E. Ward, P. Korber, and B. F. Pugh, “A packing mechanism for nucleosome organization reconstituted across a eukaryotic genome,” Science, vol. 332, no. 6032, pp. 977–980, 2011. View at Publisher · View at Google Scholar · View at Scopus
  61. I. Tirosh, N. Sigal, and N. Barkai, “Divergence of nucleosome positioning between two closely related yeast species: genetic basis and functional consequences,” Molecular Systems Biology, vol. 6, article 365, 2010. View at Publisher · View at Google Scholar · View at Scopus
  62. K. Tsui, S. Dubuis, M. Gebbia et al., “Evolution of nucleosome occupancy: conservation of global properties and divergence of gene-specific patterns,” Molecular and Cellular Biology, vol. 31, no. 21, pp. 4348–4355, 2011. View at Publisher · View at Google Scholar
  63. Y. Field, N. Kaplan, Y. Fondufe-Mittendorf et al., “Distinct modes of regulation by chromatin encoded through nucleosome positioning signals,” PLoS Computational Biology, vol. 4, no. 11, Article ID e1000216, 2008. View at Publisher · View at Google Scholar · View at Scopus
  64. N. Kaplan, I. K. Moore, Y. Fondufe-Mittendorf et al., “The DNA-encoded nucleosome organization of a eukaryotic genome,” Nature, vol. 458, no. 7236, pp. 362–366, 2009. View at Publisher · View at Google Scholar · View at Scopus
  65. K. Yen, V. Vinayachandran, K. Batta, R. T. Koerber, and B. F. Pugh, “Genome-wide nucleosome specificity and directionality of chromatin remodelers,” Cell, vol. 149, no. 7, pp. 1461–1473, 2012. View at Publisher · View at Google Scholar
  66. J. S. Beckmann and E. N. Trifonov, “Splice junctions follow a 205-base ladder,” Proceedings of the National Academy of Sciences of the United States of America, vol. 88, no. 6, pp. 2380–2383, 1991. View at Scopus
  67. P. Baldi, S. Brunak, Y. Chauvin, and A. Krogh, “Naturally occurring nucleosome positioning signals in human exons and introns,” Journal of Molecular Biology, vol. 263, no. 4, pp. 503–510, 1996. View at Publisher · View at Google Scholar · View at Scopus
  68. R. Andersson, S. Enroth, A. Rada-Iglesias, C. Wadelius, and J. Komorowski, “Nucleosomes are well positioned in exons and carry characteristic histone modifications,” Genome Research, vol. 19, no. 10, pp. 1732–1741, 2009. View at Publisher · View at Google Scholar · View at Scopus
  69. S. Schwartz, E. Meshorer, and G. Ast, “Chromatin organization marks exon-intron structure,” Nature Structural and Molecular Biology, vol. 16, no. 9, pp. 990–995, 2009. View at Publisher · View at Google Scholar · View at Scopus
  70. H. Tilgner, C. Nikolaou, S. Althammer et al., “Nucleosome positioning as a determinant of exon recognition,” Nature Structural and Molecular Biology, vol. 16, no. 9, pp. 996–1001, 2009. View at Publisher · View at Google Scholar · View at Scopus
  71. W. Chen, L. Luo, and L. Zhang, “The organization of nucleosomes around splice sites,” Nucleic Acids Research, vol. 38, no. 9, pp. 2788–2798, 2010. View at Publisher · View at Google Scholar · View at Scopus
  72. S. Schwartz and G. Ast, “Chromatin density and splicing destiny: on the cross-talk between chromatin structure and splicing,” EMBO Journal, vol. 29, no. 10, pp. 1629–1636, 2010. View at Publisher · View at Google Scholar · View at Scopus
  73. S. Kogan and E. N. Trifonov, “Gene splice sites correlate with nucleosome positions,” Gene, vol. 352, no. 1-2, pp. 57–62, 2005. View at Publisher · View at Google Scholar · View at Scopus