Biophysical Society Thematic Meeting| Les Houches 2019

Multiscale Modeling of Chromatin: Bridging Experiment with Theory

Wednesday Speaker Abstracts

STRUCTURAL STUDIES OF CHROMATIN: TOWARD UNDERSTANDING THE REGULATION OF GENOMIC DNA Hitoshi Kurumizaka 1 ; 1 The University of Tokyo, Institute for Quantitative Biosciences, Tokyo, Tokyo, Japan Objective: In eukaryotes, genomic DNA is highly compacted and accommodated in the nucleus. The genomic DNA associates with various nuclear proteins, forming a large complex called chromatin. Nucleosomes are the basic repeating units of the chromatin, which are connected by linker DNAs, and form a beads-on-a-strings appearance. In the nucleosome, two of each histone proteins, H2A, H2B, H3, and H4, form an octameric complex that left-handedly wraps about 150 base-pairs of DNA around its surface. The nucleosome formation renders the DNA inaccessible to DNA binding proteins that function in gene regulatory processes such as transcription. Therefore, DNA-binding proteins must overcome the nucleosomal barrier, when they express their functions within the chromatin. Increasing evidences suggest that versatility and dynamics of the nucleosome structure are pivotal to gene regulation, which promotes differentiation of cells in every developmental stage. However, the underlying mechanisms on how gene expression is regulated in the chromatin structure have remained elusive. Methods: We have established reconstitution systems for chromatin using purified histones. The X-ray crystallography and cryo-electron microscopy techniques are employed for structural analyses of reconstituted nucleosomes and chromatin. Results: We then studied the structural versatility of nucleosomes and chromatin, and analyzed various functional forms of chromatin. Conclusions: We solved various nucleosome and poly-nucleosome structures, and revealed how eukaryotic genes are activated or inactivated depending on the chromatin structure. These results suggest how chromatin structure and dynamics play important roles in the genomic DNA regulation.

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