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Title: The Free Energy Landscape of Internucleosome Interactions and Its Relation to Chromatin Fiber Structure

Journal Article · · ACS Central Science
 [1];  [2]; ORCiD logo [3]
  1. Univ. of Chicago, Chicago, IL (United States)
  2. Univ. of Chicago, Chicago, IL (United States); Univ. of California, Santa Barbara, CA (United States)
  3. Univ. of Chicago, Chicago, IL (United States); Argonne National Lab. (ANL), Argonne, IL (United States)

The supramolecular chromatin fiber is governed by molecular scale energetics and interactions. Such energetics originate from the fiber's building block, the nucleosome core particle (NCP). In recent years, the chromatin fiber has been examined through perturbative methods in attempts to extract the energetics of nucleosome association in the fiber. This body of work has led to different results from experiments and simulations concerning the nucleosome-nucleosome energetics. Here, we expand on previous experiments and use coarse-grained simulations to evaluate the energetics inherent to nucleosomes across a variety of parameters in configurational and environmental space. Through this effort, we are able to uncover molecular processes that are critical to understanding the 30 nm chromatin fiber structure. In particular, we describe the NCP-NCP interactions by relying on an anisotropic energetic landscape, rather than a single potential energy value. The attractions in that landscape arise predominantly from the highly anisotropic interactions provided by the NCP histone N-terminal domain (NTD) tails. Our results are found to be in good agreement with recent nucleosome interaction experiments that suggest a maximum interaction energy of 2.69kBT. Furthermore, we examine the influence of crucial epigenetic modifications, such as acetylation of the H4 tail, and how they modify the underlying landscape. Our results for acetylated NCP interactions are also in agreement with experiment. We additionally find an induced chirality in NCP-NCP interactions upon acetylation that reduces interactions which would correspond to a left-handed superhelical chromatin fiber.

Research Organization:
Argonne National Lab. (ANL), Argonne, IL (United States)
Sponsoring Organization:
National Science Foundation (NSF); USDOE
Grant/Contract Number:
AC02-06CH11357
OSTI ID:
1557994
Journal Information:
ACS Central Science, Journal Name: ACS Central Science Journal Issue: 2 Vol. 5; ISSN 2374-7943
Publisher:
American Chemical Society (ACS)Copyright Statement
Country of Publication:
United States
Language:
English

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Cited By (3)

Supramolecular multilayer organization of chromosomes: possible functional roles of planar chromatin in gene expression and DNA replication and repair journal October 2019
1CPN: A coarse-grained multi-scale model of chromatin journal June 2019
Polymer physics across scales: Modeling the multiscale behavior of functional soft materials and biological systems journal December 2019

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