skip to main content
OSTI.GOV title logo U.S. Department of Energy
Office of Scientific and Technical Information

Title: In silico evidence for sequence-dependent nucleosome sliding

Abstract

Nucleosomes represent the basic building block of chromatin and provide an important mechanism by which cellular processes are controlled. The locations of nucleosomes across the genome are not random but instead depend on both the underlying DNA sequence and the dynamic action of other proteins within the nucleus. Furthermore, these processes are central to cellular function, and the molecular details of the interplay between DNA sequence and nudeosome dynamics remain poorly understood. In this work, we investigate this interplay in detail by relying on a molecular model, which permits development of a comprehensive picture of the underlying free energy surfaces and the corresponding dynamics of nudeosome repositioning. The mechanism of nudeosome repositioning is shown to be strongly linked to DNA sequence and directly related to the binding energy of a given DNA sequence to the histone core. It is also demonstrated that chromatin remodelers can override DNA-sequence preferences by exerting torque, and the histone H4 tail is then identified as a key component by which DNA-sequence, histone modifications, and chromatin remodelers could in fact be coupled.

Authors:
ORCiD logo [1];  [2];  [3]
  1. Institute for Molecular Engineering, University of Chicago, Chicago, IL 60637,
  2. Laboratory for Molecular and Computational Genomics, Department of Chemistry, University of Wisconsin–Madison, Madison, WI 53706,, Laboratory of Genetics, University of Wisconsin–Madison, Madison, WI 53706,, UW-Biotechnology Center, University of Wisconsin–Madison, Madison, WI 53706,
  3. Institute for Molecular Engineering, University of Chicago, Chicago, IL 60637,, Materials Science Division, Argonne National Laboratory, Argonne, IL 60439
Publication Date:
Research Org.:
Argonne National Laboratory (ANL), Argonne, IL (United States)
Sponsoring Org.:
USDOE; US Department of Commerce; USDOE Office of Science (SC), Basic Energy Sciences (BES) (SC-22). Materials Sciences & Engineering Division; Midwest Integrated Center for Computational Materials (MICCoM); National Institutes of Health (NIH), National Human Genome Research Institute (NHGRI); National Institute of Standards and Technology (NIST), Center for Hierarchical Materials Design (CHiMaD)
OSTI Identifier:
1400015
Alternate Identifier(s):
OSTI ID: 1419955
Grant/Contract Number:  
AC02-06CH11357
Resource Type:
Journal Article: Published Article
Journal Name:
Proceedings of the National Academy of Sciences of the United States of America
Additional Journal Information:
Journal Name: Proceedings of the National Academy of Sciences of the United States of America Journal Volume: 114 Journal Issue: 44; Journal ID: ISSN 0027-8424
Publisher:
Proceedings of the National Academy of Sciences
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; advanced sampling techniques; chromatin dynamics; molecular simulation; nudeosome repositioning

Citation Formats

Lequieu, Joshua, Schwartz, David C., and de Pablo, Juan J. In silico evidence for sequence-dependent nucleosome sliding. United States: N. p., 2017. Web. doi:10.1073/pnas.1705685114.
Lequieu, Joshua, Schwartz, David C., & de Pablo, Juan J. In silico evidence for sequence-dependent nucleosome sliding. United States. https://doi.org/10.1073/pnas.1705685114
Lequieu, Joshua, Schwartz, David C., and de Pablo, Juan J. 2017. "In silico evidence for sequence-dependent nucleosome sliding". United States. https://doi.org/10.1073/pnas.1705685114.
@article{osti_1400015,
title = {In silico evidence for sequence-dependent nucleosome sliding},
author = {Lequieu, Joshua and Schwartz, David C. and de Pablo, Juan J.},
abstractNote = {Nucleosomes represent the basic building block of chromatin and provide an important mechanism by which cellular processes are controlled. The locations of nucleosomes across the genome are not random but instead depend on both the underlying DNA sequence and the dynamic action of other proteins within the nucleus. Furthermore, these processes are central to cellular function, and the molecular details of the interplay between DNA sequence and nudeosome dynamics remain poorly understood. In this work, we investigate this interplay in detail by relying on a molecular model, which permits development of a comprehensive picture of the underlying free energy surfaces and the corresponding dynamics of nudeosome repositioning. The mechanism of nudeosome repositioning is shown to be strongly linked to DNA sequence and directly related to the binding energy of a given DNA sequence to the histone core. It is also demonstrated that chromatin remodelers can override DNA-sequence preferences by exerting torque, and the histone H4 tail is then identified as a key component by which DNA-sequence, histone modifications, and chromatin remodelers could in fact be coupled.},
doi = {10.1073/pnas.1705685114},
url = {https://www.osti.gov/biblio/1400015}, journal = {Proceedings of the National Academy of Sciences of the United States of America},
issn = {0027-8424},
number = 44,
volume = 114,
place = {United States},
year = {Wed Oct 18 00:00:00 EDT 2017},
month = {Wed Oct 18 00:00:00 EDT 2017}
}

Journal Article:
Free Publicly Available Full Text
Publisher's Version of Record at https://doi.org/10.1073/pnas.1705685114

Citation Metrics:
Cited by: 46 works
Citation information provided by
Web of Science

Save / Share:

Works referenced in this record:

Mobile nucleosomes--a general behavior.
journal, August 1992


Solvent Mediated Interactions in the Structure of the Nucleosome Core Particle at 1.9Å Resolution
journal, June 2002


Revisiting the finite temperature string method for the calculation of reaction tubes and free energies
journal, May 2009


Human diseases with underlying defects in chromatin structure and modification
journal, October 2001


Dynamics of Nucleosome Invasion by DNA Binding Proteins
journal, August 2011


A genomic code for nucleosome positioning
journal, July 2006


Effect of force on mononucleosomal dynamics
journal, October 2006


Chromatin remodeling by ISW2 and SWI/SNF requires DNA translocation inside the nucleosome
journal, March 2006


Telomeric Nucleosomes Are Intrinsically Mobile
journal, June 2007


Using DNA mechanics to predict in vitro nucleosome positions and formation energies
journal, June 2009


Multidimensional free-energy calculations using the weighted histogram analysis method
journal, November 1995


Mapping nucleosome position at single base-pair resolution by using site-directed hydroxyl radicals.
journal, February 1996


Intrinsic histone-DNA interactions are not the major determinant of nucleosome positions in vivo
journal, July 2009


Rigid-body molecular dynamics of DNA inside a nucleosome
journal, March 2013


The main role of the sequence-dependent DNA elasticity in determining the free energy of nucleosome formation on telomeric DNAs
journal, January 2000


Mobility of positioned nucleosomes on 5 S rDNA
journal, July 1991


Nucleosome sliding mechanisms: new twists in a looped history
journal, September 2013


An experimentally-informed coarse-grained 3-site-per-nucleotide model of DNA: Structure, thermodynamics, and dynamics of hybridization
journal, October 2013


Frustration, specific sequence dependence, and nonlinearity in large-amplitude fluctuations of allosteric proteins
journal, February 2011


In vitro low propensity to form nucleosomes of four telomeric sequences
journal, January 1997


Nucleosomes in Solution Exist as a Mixture of Twist-defect States
journal, January 2005


Mechanisms of ATP-dependent nucleosome sliding
journal, February 2010


The chromatin remodeller ACF acts as a dimeric motor to space nucleosomes
journal, December 2009


Dynamics of nucleosome remodelling by individual ACF complexes
journal, December 2009


Positioning and stability of nucleosomes on MMTV 3′LTR sequences
journal, January 1998


ISWI Remodelers Slide Nucleosomes with Coordinated Multi-Base-Pair Entry Steps and Single-Base-Pair Exit Steps
journal, January 2013


Nucleosome structural studies
journal, February 2011


DNA Shape Dominates Sequence Affinity in Nucleosome Formation
journal, October 2014


The ATPase domain of ISWI is an autonomous nucleosome remodeling machine
journal, December 2012


Transcription factor access is mediated by accurately positioned nucleosomes on the mouse mammary tumor virus promoter
journal, February 1991


Coarse-Grained Ions for Nucleic Acid Modeling
journal, October 2015


High-resolution dynamic mapping of histone-DNA interactions in a nucleosome
journal, January 2009


Rapid spontaneous accessibility of nucleosomal DNA
journal, December 2004


Crystal structure of the nucleosome core particle at 2.8 Å resolution
journal, September 1997


Single-base resolution mapping of H1-nucleosome interactions and 3D organization of the nucleosome
journal, May 2010


Histone H4 tail mediates allosteric regulation of nucleosome remodelling by linker DNA
journal, June 2014


Coarse-grained modeling of DNA curvature
journal, October 2014


Defining the axis of a helix
journal, January 1989


New DNA sequence rules for high affinity binding to histone octamer and sequence-directed nucleosome positioning
journal, February 1998


Are nucleosome positions in vivo primarily determined by histone–DNA sequence preferences?
journal, November 2009


Blocking Transcription Through a Nucleosome with Synthetic DNA Ligands
journal, August 2002


The DNA-encoded nucleosome organization of a eukaryotic genome
journal, December 2008


ACF, an ISWI-Containing and ATP-Utilizing Chromatin Assembly and Remodeling Factor
journal, July 1997


The chromatin-remodeling enzyme ACF is an ATP-dependent DNA length sensor that regulates nucleosome spacing
journal, November 2006


Chromatin remodeling by DNA bending, not twisting
journal, January 2005


Covalent modifications of histones during development and disease pathogenesis
journal, November 2007


Dynamic Regulation of Nucleosome Positioning in the Human Genome
journal, March 2008


Disparity in the DNA translocase domains of SWI/SNF and ISW2
journal, January 2012


Nucleosome dynamics: Sequence matters
journal, June 2016


Determinants of nucleosome positioning
journal, March 2013


Chromatin Dynamics: Nucleosomes go Mobile through Twist Defects
journal, October 2003


Polymer Reptation and Nucleosome Repositioning
journal, May 2001


Umbrella sampling: Umbrella sampling
journal, May 2011


Artificial nucleosome positioning sequences.
journal, October 1989


The structure of DNA in the nucleosome core
journal, May 2003


A Mesoscale Model of DNA and Its Renaturation
journal, March 2009


ISWI Remodelling of Physiological Chromatin Fibres Acetylated at Lysine 16 of Histone H4
journal, February 2014


Simplified and improved string method for computing the minimum energy paths in barrier-crossing events
journal, April 2007


Sequence motifs and free energies of selected natural and non-natural nucleosome positioning DNA sequences
journal, April 1999


Crystal Structures of Nucleosome Core Particles in Complex with Minor Groove DNA-binding Ligands
journal, February 2003


Determinants of nucleosome organization in primary human cells
journal, May 2011


Nucleosome Repositioning via Loop Formation
journal, May 2003


Chromatin remodelling at promoters suppresses antisense transcription
journal, December 2007


A coarse grain model for DNA
journal, February 2007


Analysis of Nucleosome Repositioning by Yeast ISWI and Chd1 Chromatin Remodeling Complexes
journal, April 2006


A Novel Roll-and-Slide Mechanism of DNA Folding in Chromatin: Implications for Nucleosome Positioning
journal, August 2007


Nucleosome hopping and sliding kinetics determined from dynamics of single chromatin fibers in Xenopus egg extracts
journal, August 2007


A highly conserved repetitive DNA sequence, (TTAGGG)n, present at the telomeres of human chromosomes.
journal, September 1988


Tension-Dependent Free Energies of Nucleosome Unwrapping
journal, August 2016


Chromatin Remodeling In Vivo
journal, November 2003


A 'loop recapture' mechanism for ACF-dependent nucleosome remodeling
journal, July 2005