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Title: In silico evidence for sequence-dependent nucleosome sliding

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. Univ. of Chicago, Chicago, IL (United States)
  2. Univ. of Wisconsin-Madison, Madison, WI (United States)
  3. Univ. of Chicago, Chicago, IL (United States); Argonne National Lab. (ANL), Argonne, IL (United States)
Publication Date:
Grant/Contract Number:
AC02-06CH11357
Type:
Published Article
Journal Name:
Proceedings of the National Academy of Sciences of the United States of America
Additional Journal Information:
Journal Volume: 114; Journal Issue: 44; Journal ID: ISSN 0027-8424
Publisher:
National Academy of Sciences, Washington, DC (United States)
Research Org:
Argonne National Lab. (ANL), Argonne, IL (United States)
Sponsoring Org:
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); USDOE
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; advanced sampling techniques; chromatin dynamics; molecular simulation; nudeosome repositioning
OSTI Identifier:
1400015
Alternate Identifier(s):
OSTI ID: 1419955