120th General Meeting of the KCS

Type Oral Presentation
Area Oral Presentation for Young Scholars in Physical Chemistry
Room No. Room 208+209+210
Time THU 09:00-:
Code PHYS.O-1
Subject High-throughput simulations and single-molecule experiments reveal DNA looping and self-association controlled by sequence and methylation
Authors Jejoong Yoo, Sangwoo Park1, Taekjip Ha1, Aleksei Aksimentiev2,*
Center for self-assembly and complexity, Institute for basic science, Korea
1Johns Hopkins University, USA, United States
2University of Illinois at Urbana-Champaign, United States
Abstract Human chromosomes have long been thought to behave like random polymers encapsulated in a nuclear envelop. However, it is becoming more and more clear that that chromosomes organize into certain three-dimensional structures that dynamically change depending on the cell’s state. The very presence of such structures implies that yet unknown physical interactions govern the free energy change in the process of cell development and cancer. To find a clue about the mystery, we determined the free energy landscape of a nucleosome---the fundamental structural unit of chromosome that consists of a fragment of DNA wrapped around a protein core. Technically, we combined high-throughput molecular dynamics simulations and single-molecule experiments. At a single nucleosome level, we found both sequence and CpG methylation of DNA to uniquely determine the orientation of the DNA loop with respect to the protein core. This finding offers a simple physical mechanism of controlling DNA accessibility to RNA polymerases. At a multi-nucleosome level, we found the AT content of the DNA sequence and the methylation of either DNA or the nucleosome proteins to govern association of nucleosomes into clusters. Overall, our findings suggest that DNA is a remarkable polymer that can program its own free energy landscape by sequence and methylation to regulate the nucleus-scale organization of chromosomes.
E-mail jejoong@gmail.com