Sequence-dependent nucleosome sliding in rotation-coupled and uncoupled modes revealed by molecular simulations

While nucleosome positioning on eukaryotic genome play important roles for genetic regulation, molecular mechanisms of nucleosome positioning and sliding along DNA are not well understood. Here we investigated thermally-activated spontaneous nucleosome sliding mechanisms developing and applying a coarse-grained molecular simulation method that incorporates both long-range electrostatic and short-range hydrogen-bond interactions between histone octamer and DNA. The simulations revealed two distinct sliding modes depending on the nucleosomal DNA sequence. A uniform DNA sequence showed frequent sliding with one base pair step in a rotation-coupled manner, akin to screw-like motions. On the contrary, a strong positioning sequence, the so-called 601 sequence, exhibits rare, abrupt transitions of five and ten base pair steps without rotation. Moreover, we evaluated the importance of hydrogen bond interactions on the sliding mode, finding that strong and weak bonds favor respectively the rotation-coupled and -uncoupled sliding movements.

[1]  Yaniv Lubling,et al.  Distinct Modes of Regulation by Chromatin Encoded through Nucleosome Positioning Signals , 2008, PLoS Comput. Biol..

[2]  Shoji Takada,et al.  RESPAC: Method to Determine Partial Charges in Coarse-Grained Protein Model and Its Application to DNA-Binding Proteins. , 2014, Journal of chemical theory and computation.

[3]  Roland L. Dunbrack,et al.  proteins STRUCTURE O FUNCTION O BIOINFORMATICS Improved prediction of protein side-chain conformations with SCWRL4 , 2022 .

[4]  Alexander Goncearenco,et al.  Coupling between Histone Conformations and DNA Geometry in Nucleosomes on a Microsecond Timescale: Atomistic Insights into Nucleosome Functions. , 2016, Journal of molecular biology.

[5]  Frank Noé,et al.  Markov models of molecular kinetics: generation and validation. , 2011, The Journal of chemical physics.

[6]  Aakrosh Ratan,et al.  Energy landscape and multiroute folding of topologically complex proteins adenylate kinase and 2 ouf-knot , 2012 .

[7]  Helmut Schiessel,et al.  Theory of nucleosome corkscrew sliding in the presence of synthetic DNA ligands. , 2004, Journal of molecular biology.

[8]  J. Widom,et al.  Nucleosomes facilitate their own invasion , 2004, Nature Structural &Molecular Biology.

[9]  T. Richmond,et al.  The structure of DNA in the nucleosome core , 2003, Nature.

[10]  M. Parrinello,et al.  Well-tempered metadynamics: a smoothly converging and tunable free-energy method. , 2008, Physical review letters.

[11]  Massimiliano Bonomi,et al.  PLUMED 2: New feathers for an old bird , 2013, Comput. Phys. Commun..

[12]  Massimiliano Bonomi,et al.  Reconstructing the equilibrium Boltzmann distribution from well‐tempered metadynamics , 2009, J. Comput. Chem..

[13]  Andrew Flaus,et al.  Sin mutations alter inherent nucleosome mobility , 2004, The EMBO journal.

[14]  Eran Segal,et al.  From DNA sequence to transcriptional behaviour: a quantitative approach , 2009, Nature Reviews Genetics.

[15]  J Seth Strattan,et al.  Removal of promoter nucleosomes by disassembly rather than sliding in vivo. , 2004, Molecular cell.

[16]  Janet Iwasa,et al.  Mechanisms of action and regulation of ATP-dependent chromatin-remodelling complexes , 2017, Nature Reviews Molecular Cell Biology.

[17]  Thomas C. Bishop,et al.  Atomistic simulations of nucleosomes , 2013 .

[18]  Shoji Takada,et al.  Energy landscape and multiroute folding of topologically complex proteins adenylate kinase and 2ouf-knot , 2012, Proceedings of the National Academy of Sciences.

[19]  Juan J de Pablo,et al.  An experimentally-informed coarse-grained 3-Site-Per-Nucleotide model of DNA: structure, thermodynamics, and dynamics of hybridization. , 2013, The Journal of chemical physics.

[20]  Juan J de Pablo,et al.  In silico evidence for sequence-dependent nucleosome sliding , 2017, Proceedings of the National Academy of Sciences.

[21]  E. M. Bradbury,et al.  Mobile nucleosomes‐‐a general behavior. , 1992, The EMBO journal.

[22]  Xiang-Jun Lu,et al.  3DNA: a versatile, integrated software system for the analysis, rebuilding and visualization of three-dimensional nucleic-acid structures , 2008, Nature Protocols.

[23]  Yamini Dalal,et al.  Shearing of the CENP-A dimerization interface mediates plasticity in the octameric centromeric nucleosome , 2015, Scientific Reports.

[24]  Wilma K. Olson,et al.  DNA Simulation Benchmarks as Revealed by X-Ray Structures , 2006 .

[25]  Alexandre V. Morozov,et al.  Using DNA mechanics to predict in vitro nucleosome positions and formation energies , 2009, Nucleic acids research.

[26]  Karolin Luger,et al.  New insights into nucleosome and chromatin structure: an ordered state or a disordered affair? , 2012, Nature Reviews Molecular Cell Biology.

[27]  S H Yoshimura,et al.  Histone core slips along DNA and prefers positioning at the chain end. , 2001, Physical review letters.

[28]  J. Widom,et al.  New DNA sequence rules for high affinity binding to histone octamer and sequence-directed nucleosome positioning. , 1998, Journal of molecular biology.

[29]  E.Y.D. Chua,et al.  Crystal structures of nucleosome core particles containing the '601' strong positioning sequence. , 2010, Journal of molecular biology.

[30]  Jörg Langowski,et al.  Nucleosome disassembly intermediates characterized by single-molecule FRET , 2009, Proceedings of the National Academy of Sciences.

[31]  D. Case,et al.  PARMBSC1: A REFINED FORCE-FIELD FOR DNA SIMULATIONS , 2015, Nature Methods.

[32]  Andrew Flaus,et al.  Dynamic Properties of Nucleosomes during Thermal and ATP-Driven Mobilization , 2003, Molecular and Cellular Biology.

[33]  Shoji Takada,et al.  Partial Unwrapping and Histone Tail Dynamics in Nucleosome Revealed by Coarse-Grained Molecular Simulations , 2015, PLoS Comput. Biol..

[34]  T. Richmond,et al.  Solvent mediated interactions in the structure of the nucleosome core particle at 1.9 a resolution. , 2002, Journal of molecular biology.

[35]  Shoji Takada,et al.  Dynamic Coupling among Protein Binding, Sliding, and DNA Bending Revealed by Molecular Dynamics. , 2016, Journal of the American Chemical Society.

[36]  F. Thoma,et al.  Poly(dA).poly(dT) rich sequences are not sufficient to exclude nucleosome formation in a constitutive yeast promoter. , 1990, Nucleic acids research.

[37]  Shoji Takada,et al.  Histone acetylation dependent energy landscapes in tri-nucleosome revealed by residue-resolved molecular simulations , 2016, Scientific Reports.

[38]  David Chandler,et al.  Transition path sampling: throwing ropes over rough mountain passes, in the dark. , 2002, Annual review of physical chemistry.

[39]  Peter G Wolynes,et al.  Exploring the Free Energy Landscape of Nucleosomes. , 2016, Journal of the American Chemical Society.

[40]  K. Struhl,et al.  Determinants of nucleosome positioning , 2013, Nature Structural &Molecular Biology.

[41]  J. Widom,et al.  Polymer reptation and nucleosome repositioning. , 2001, Physical review letters.

[42]  Shoji Takada,et al.  CafeMol: A Coarse-Grained Biomolecular Simulator for Simulating Proteins at Work. , 2011, Journal of chemical theory and computation.

[43]  Oliver Beckstein,et al.  MDAnalysis: A toolkit for the analysis of molecular dynamics simulations , 2011, J. Comput. Chem..

[44]  T. Richmond,et al.  Crystal structure of the nucleosome core particle at 2.8 Å resolution , 1997, Nature.

[45]  A. Laio,et al.  Metadynamics: a method to simulate rare events and reconstruct the free energy in biophysics, chemistry and material science , 2008 .

[46]  E. O’Shea,et al.  A quantitative model of transcription factor–activated gene expression , 2008, Nature Structural &Molecular Biology.

[47]  Dimitris Thanos,et al.  Nucleosome Sliding via TBP DNA Binding In Vivo , 2001, Cell.

[48]  James W. Murray,et al.  High–quality protein backbone reconstruction from alpha carbons using Gaussian mixture models , 2013, J. Comput. Chem..

[49]  Shoji Takada,et al.  Multiscale ensemble modeling of intrinsically disordered proteins: p53 N-terminal domain. , 2011, Biophysical journal.

[50]  H. Schiessel,et al.  Chromatin dynamics: nucleosomes go mobile through twist defects. , 2003, Physical review letters.

[51]  Karolin Luger,et al.  Blocking transcription through a nucleosome with synthetic DNA ligands. , 2002, Journal of molecular biology.

[52]  Zhenhai Li,et al.  Distinct Roles of Histone H3 and H2A Tails in Nucleosome Stability , 2016, Scientific Reports.

[53]  W. Olson,et al.  Nucleosome-free DNA regions differentially affect distant communication in chromatin , 2016, Nucleic acids research.

[54]  Berk Hess,et al.  GROMACS: High performance molecular simulations through multi-level parallelism from laptops to supercomputers , 2015 .

[55]  Shoji Takada,et al.  Modeling Structural Dynamics of Biomolecular Complexes by Coarse-Grained Molecular Simulations. , 2015, Accounts of chemical research.

[56]  Shoji Takada,et al.  Near-atomic structural model for bacterial DNA replication initiation complex and its functional insights , 2016, Proceedings of the National Academy of Sciences.

[57]  Irene K. Moore,et al.  A genomic code for nucleosome positioning , 2006, Nature.

[58]  Tamar Schlick,et al.  Hierarchical looping of zigzag nucleosome chains in metaphase chromosomes , 2016, Proceedings of the National Academy of Sciences.

[59]  E. Segal,et al.  Poly(da:dt) Tracts: Major Determinants of Nucleosome Organization This Review Comes from a Themed Issue on Protein-nucleic Acid Interactions Edited , 2022 .

[60]  Juan J de Pablo,et al.  Coarse-grained modeling of DNA curvature. , 2014, The Journal of chemical physics.

[61]  Shoji Takada,et al.  Energy landscape views for interplays among folding, binding, and allostery of calmodulin domains , 2014, Proceedings of the National Academy of Sciences.

[62]  Juan J de Pablo,et al.  DNA shape dominates sequence affinity in nucleosome formation. , 2014, Physical review letters.