Abstract.
Roughly 3/4 of human genomes are sequestered by nucleosomes, DNA spools with a protein core, dictating a broad range of biological processes, ranging from gene regulation, recombination, and replication, to chromosome condensation. Nucleosomes are dynamical structures and temporarily expose wrapped DNA through spontaneous unspooling from either end, a process called site exposure or nucleosome breathing. Here we ask how this process is influenced by the mechanical properties of the wrapped DNA, which is known to depend on the underlying base pair sequence. Using a coarse-grained nucleosome model we calculate the accessibility profiles for site exposure. We find that the process is very sensitive to sequence effects, so that evolution could potentially tune the accessibility of nucleosomal DNA and would only need a small number of mutations to do so.
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K. Luger, A.W. Mäder, R.K. Richmond, D.F. Sargent, T.J. Richmond, Nature 389, 6648 (1997)
C.A. Davey, D.F. Sargent, K. Luger, A.W. Mäder, T.J. Richmond, J. Mol. Biol. 319, 1097 (2002)
B. Eslami-Mossallam, H. Schiessel, J. van Noort, Adv. Colloid Interface Sci. 232, 101 (2016)
K. Struhl, E. Segal, Nat. Struct. Mol. Biol. 20, 267 (2013)
E. Segal, Y. Fondufe-Mittendorf, L. Chen, A. Thaström, Y. Field, I.K. Moore et al., Nature 442, 772 (2006)
E.N. Trifonov, J.L. Sussman, Proc. Natl. Acad. Sci. U.S.A. 77, 3816 (1980)
S.C. Satchwell, H.R. Drew, A.A. Travers, J. Mol. Biol. 191, 659 (1986)
B. Eslami-Mossallam, R.D. Schram, M. Tompitak, J. van Noort, H. Schiessel, PLoS ONE 11, e0156905 (2016)
N. Kaplan, I.K. Moore, Y. Fondufe-Mittendorf, A.J. Gossett, D. Tillo, Y. Field et al., Nature 458, 362 (2009)
M. Tompitak, C. Vaillant, H. Schiessel, Biophys. J. 112, 505 (2017)
T. Vavouri, B. Lehner B, PLoS Genet. 7, e1002036 (2011)
G. Drillon, B. Audit, F. Argoul, A. Arneodo, BMC Genomics 17, 526 (2016)
T.T.M. Ngo, Q. Zhang, R. Zhou, J.G. Yodh, T. Ha, Cell 160, 1135 (2015)
L. de Bruin, M. Tompitak, B. Eslami-Mossallam, H. Schiessel, J. Phys. Chem. B 120, 5855 (2016)
M.A. Hall, A. Shundrovsky, L. Bai, R.M. Fulbright, J.T. Lis, M.D. Wang, Nature Struct. Mol. Biol. 16, 124 (2009)
V.A. Bondarenko, L.M. Steele, A. Ujvari, D.A. Gaykolova, O.I. Kulaeva, Y.S. Polikanov, D.S. Luse, V.M. Studitsky, Mol. Cell 24, 469 (2006)
K. Polach, J. Widom, J. Mol. Biol. 254, 130 (1995)
J. Anderson, J. Widom, J. Mol. Biol. 296, 979 (2000)
K. Polach, P. Lowary, J. Widom, J. Mol. Biol. 298, 211 (2000)
M. Tompitak, L. de Bruin, B. Eslami-Mossallam, H. Schiessel, Phys. Rev. E 95, 052402 (2017)
J.A.J. Wondergem, H. Schiessel, M. Tompitak, J. Chem. Phys. 147, 174101 (2017)
G. Li, J. Widom, Nat. Struct. Mol. Biol. 11, 763 (2004)
G. Li, M. Levitus, C. Bustamante, J. Widom, Nat. Struct. Mol. Biol. 12, 46 (2005)
H.S. Tims, K. Gurunathan, M. Levitus, J. Widom, J. Mol. Biol. 411, 430 (2011)
V. Böhm, A.R. Hieb, A.J. Andrews, A. Gansen, A. Rocker, K. Tóth et al., Nucl. Acids. Res. 39, 3093 (2011)
G. Moyle-Heyrman, H.S. Tims, J. Widom, J. Mol. Biol. 412, 634 (2011)
K. Tóth, V. Böhm, C. Sellmann, M. Danner, J. Hanne, M. Berg et al., Cytometry A 83, 839 (2013)
M. Tomschik, H. Zheng, K. van Holde, J. Zlatanova, S.H. Leuba, Proc. Natl. Acad. Sci. U.S.A. 102, 3278 (2005)
L. Kelbauskas, N. Chan, R. Bash, J. Yodh, N. Woodbury, D. Lohr, Biochemistry 46, 2239 (2007)
W.J.A. Koopmans, A. Brehm, C. Logie, T. Schmidt, J. van Noort, J. Fluoresc. 17, 785 (2007)
L. Kelbauskas, J. Sun, N. Woodbury, D. Lohr, Biochemistry 47, 9627 (2008)
L. Kelbauskas, N. Woodbury, D. Lohr, Biochem. Cell Biol. 87, 323 (2009)
A. Gansen, K. Tóth, N. Schwarz, J. Langowski, J. Phys. Chem. B 113, 2604 (2009)
A. Gansen, A. Valeri, F. Hauger, S. Felekyan, S. Kalinin, K. Tóth et al., Proc. Natl. Acad. Sci. U.S.A. 106, 15308 (2009)
W.J.A. Koopmans, R. Buning, T. Schmidt, J. van Noort, Biophys. J. 97, 195 (2009)
J.A. North, J.C. Shimko, S. Javaid, A.M. Mooney, M.A. Shoffner, S.D. Rose, R. Bundschuh, R. Fishel, J.J. Ottesen, M.G. Poirier, Nucl. Acids Res. 40, 10215 (2012)
I. Jimenez-Useche, C. Yuan, Biophys. J. 103, 2502 (2012)
A. Gansen, A.R. Hieb, V. Böhm, K. Tóth, J. Langowski, PLoS One 8, e57018 (2013)
A.R. Hieb, A. Gansen, V. Böhm, J. Langowski, Nucl. Acids Res. 42, 7561 (2014)
A. Gansen, K. Tóth, N. Schwarz, J. Langowski, Nucl. Acids. Res. 43, 1433 (2015)
N.P. Hazan, T.E. Tomov, R. Tsukanov, M. Liber, Y. Berger, R. Masoud, K. Toth, J. Langowski, E. Nir, Biophys. J. 109, 1676 (2015)
J.V. Le, Y. Luo, M.A. Darcy, C.R. Lucas, M.F. Goodwin, M.G. Poirier, C.E. Castro, ACS Nano 10, 7073 (2016)
M.D. Gibson, J. Gatchalian, A. Slater, T.G. Kutateladze, M.G. Poirier, Nucl. Acids Res. 45, 3767 (2017)
R. Buning, J. van Noort, Biochimie 92, 1729 (2010)
L. Lenz, M. Hoenderdos, P. Prinsen, H. Schiessel, J. Phys.: Condens. Matter 27, 064104 (2015)
R.U. Protacio, K.J. Polach, J. Widom, J. Mol. Biol. 274, 708 (1997)
J.D. Anderson, P.T. Lowary, J. Widom, J. Mol. Biol. 307, 977 (2001)
J.D. Anderson, J. Widom, Mol. Cell. Biol. 21, 3830 (2001)
K. Polach, J. Widom, J. Mol. Biol. 258, 800 (1996)
W. Möbius, R.A. Neher, U. Gerland, Phys. Rev. Lett. 97, 208102 (2006)
P. Prinsen, H. Schiessel, Biochimie 92, 1722 (2010)
L.A. Mirny, Proc. Natl. Acad. Sci. U.S.A. 107, 22534 (2010)
B. van Opheusden, F. Redig, H. Schiessel, J. Phys. A: Math. Theor. 46, 095005 (2013)
W. Möbius, B. Osberg, A.M. Tsankov, O.J. Rando, U. Gerland, Proc. Natl. Acad. Sci. U.S.A. 110, 5719 (2013)
S. Marzen, H.G. Garcia, R. Phillips, J. Mol. Biol. 425, 1433 (2013)
H. Kenzaki, S. Takada, PLoS Comput. Biol. 11, e1004443 (2015)
V. Teif, R. Ettig, K. Rippe, Biophys. J. 99, 2597 (2010)
R.V. Chereji, A.V. Morozov, Proc. Natl. Acad. Sci. U.S.A. 111, 5236 (2014)
W.K. Olson, A.A. Gorin, X.-J. Lu, L.M. Hock, V.B. Zhurkin, Proc. Natl. Acad. Sci. U.S.A. 95, 11163 (1998)
F. Lankaš, J. Sponer, J. Langowski, T.E. Cheatham III, Biophys. J. 85, 2872 (2003)
N.B. Becker, L. Wolff, R. Everaers, Nucl. Acids Res. 34, 5638 (2006)
A. Fathizadeh, A.B. Besya, M.R. Ejtehadi, H. Schiessel, Eur. Phys. J. E 36, 1 (2013)
M. Tompitak, G. Barkema, H. Schiessel, BMC Bioinform. 18, 157 (2017)
P.T. Lowary, J. Widom, J. Mol. Biol. 276, 19 (1998)
R.T. Simpson, D.W. Stafford, Proc. Natl. Acad. Sci. U.S.A. 80, 51 (1983)
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Culkin, J., de Bruin, L., Tompitak, M. et al. The role of DNA sequence in nucleosome breathing. Eur. Phys. J. E 40, 106 (2017). https://doi.org/10.1140/epje/i2017-11596-2
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DOI: https://doi.org/10.1140/epje/i2017-11596-2