한빛사 논문
Jejoong Yoo1,*, Sangwoo Park3, Christopher Maffeo2, Taekjip Ha3,4,* and Aleksei Aksimentiev2,5,*
1Department of Physics, Sungkyunkwan University, Suwon 16419, Republic of Korea, 2Department of Physics and the Center for the Physics of Living Cells, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA, 3Department of Biophysics and Biophysical Chemistry, Johns Hopkins University, Baltimore, MD 21205, USA, 4Howard Hughes Medical Institute, Baltimore, MD 21218, USA and 5Beckman Institute for Advanced Science and Technology, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA
*Corresponding author.
Abstract
Eukaryotic genome and methylome encode DNA fragments’ propensity to form nucleosome particles. Although the mechanical properties of DNA possibly orchestrate such encoding, the definite link between ‘omics’ and DNA energetics has remained elusive. Here, we bridge the divide by examining the sequence-dependent energetics of highly bent DNA. Molecular dynamics simulations of 42 intact DNA minicircles reveal that each DNA minicircle undergoes inside-out conformational transitions with the most likely configuration uniquely prescribed by the nucleotide sequence and methylation of DNA. The minicircles’ local geometry consists of straight segments connected by sharp bends compressing the DNA’s inward-facing major groove. Such an uneven distribution of the bending stress favors minimum free energy configurations that avoid stiff base pair sequences at inward-facing major grooves. Analysis of the minicircles’ inside-out free energy landscapes yields a discrete worm-like chain model of bent DNA energetics that accurately account for its nucleotide sequence and methylation. Experimentally measuring the dependence of the DNA looping time on the DNA sequence validates the model. When applied to a nucleosome-like DNA configuration, the model quantitatively reproduces yeast and human genomes’ nucleosome occupancy. Further analyses of the genome-wide chromatin structure data suggest that DNA bending energetics is a fundamental determinant of genome architecture.
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