Mechanical properties of symmetric and asymmetric DNA A-tracts: implications for looping and nucleosome positioning.
A-tracts are functionally important DNA sequences which induce helix bending and have peculiar structural properties. While A-tract structure has been qualitatively well characterized, their mechanical properties remain controversial. A-tracts appear structurally rigid and resist nucleosome formation, but seem flexible in DNA looping. In this work, we investigate mechanical properties of symmetric AnTn and asymmetric A2n tracts for n = 3, 4, 5 using two types of coarse-grained models. The first model represents DNA as an ensemble of interacting rigid bases with non-local quadratic deformation energy, the second one treats DNA as an anisotropically bendable and twistable elastic rod. Parameters for both models are inferred from microsecond long, atomic-resolution molecular dynamics simulations. We find that asymmetric A-tracts are more rigid than the control G/C-rich sequence in localized distortions relevant for nucleosome formation, but are more flexible in global bending and twisting relevant for looping. The symmetric tracts, in contrast, are more rigid than asymmetric tracts and the control, both locally and globally. Our results can reconcile the contradictory stiffness data on A-tracts and suggest symmetric A-tracts to be more efficient in nucleosome exclusion than the asymmetric ones. This would open a new possibility of gene expression manipulation using A-tracts.
Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, Flemingovo nám. 2, 16610 Prague, Czech Republic Institute of Biophysics, Academy of Sciences of the Czech Republic, Královopolská 135, 61265 Brno, Czech Republic.
Tomáš
T
Dršata
Institute of Biophysics, Academy of Sciences of the Czech Republic, Královopolská 135, 61265 Brno, Czech Republic.
Nada
N
Špačková
Regional Centre of Advanced Technologies and Materials, Department of Physical Chemistry, Faculty of Science, Palacký University, 17. listopadu 12, 77146 Olomouc, Czech Republic.
Petr
P
Jurečka
Regional Centre of Advanced Technologies and Materials, Department of Physical Chemistry, Faculty of Science, Palacký University, 17. listopadu 12, 77146 Olomouc, Czech Republic.
Marie
M
Zgarbová
Institute of Biophysics, Academy of Sciences of the Czech Republic, Královopolská 135, 61265 Brno, Czech Republic CEITEC-Central European Institute of Technology, Campus Bohunice, Kamenice 5, 62500 Brno, Czech Republic.
Jiří
J
Šponer
Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, Flemingovo nám. 2, 16610 Prague, Czech Republic filip.lankas@uochb.cas.cz.
Filip
F
Lankaš
D000225:Adenine / Q000737:chemistry; D001483:Base Sequence; D001696:Biomechanical Phenomena; D004247:DNA / Q000737:chemistry*; D019277:Entropy; D056004:Molecular Dynamics Simulation; D009690:Nucleic Acid Conformation; D009707:Nucleosomes / Q000737:chemistry*; D011061:Poly A / Q000737:chemistry
D009707:Nucleosomes; D011061:Poly A; D004247:DNA; D000225:Adenine