Biophysical Society Thematic Meeting| Santa Cruz 2018

Genome Biophysics: Integrating Genomics and Biophysics to Understand Structural and Functional Aspects of Genomes

Poster Abstracts

19-POS Board 19 Epigenetically Controlled Phase Behaviors of DNA Revealed by Multi-scale Molecular

Dynamics Simulations and Single-Molecule Experiments Jejoong Yoo 1 , Hajin Kim 3,1 , Taekjip Ha 4 , Aleksei Aksimentiev 2 .

1 Institute for Basic Science, Pohang, South Korea, 2 University of Illinois at Urbana-Champaign, Urbana, IL, USA, 3 Ulsan National Institute of Science and Technology, Ulsan, South Korea, 4 Johns Hopkins University, Baltimore, MD, USA. Historically, it was believed that the phase behavior would not play a role in biology as important as in physics. However, recent findings that biological protein or RNA systems can experience the phase separation are dramatically changing our general views on the phase behavior in biology. Especially, those findings raise a possibility that DNA molecules might also exhibit phase behaviors, which can directly affect the organization of human chromosomes that consist of compacted heterochromatin and loosely folded euchromatin. Here, we demonstrate that DNA in a polyelectrolyte solution of polyamine or lysine peptides can indeed form separate phases depending on sequences and epigenetic modifications by combining multi-scale molecular dynamics (MD) simulations and single-molecule experiments. First, we show that the condensation force of hundreds base pair-long DNA molecules monotonically increases as the AT content of DNA increases. Interestingly, methylations of cytosine and/or lysine peptides could enhance the formation of condensed phase. Further, we also show that the compactness of kilo-base pairs-long bacterial genes is controlled by the AT contents of the genes: the higher AT contents the smaller radius of gyration. The fact that the compactness of synonymous genes can be simply controlled by adjusting the AT content suggests a new evolutionary role of wobble bases in gene activities. Overall, our findings suggest a novel epigenetic mechanism that can contribute to the mechanical regulation of nucleus-scale organization of chromosomes.

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