CDS/CIMMS Lunchtime Seminar: Understanding chromatin folding and regulation through mesoscale modeling and simulation

Dr. Gaurav Arya, Department of Nanoengineering, University of California, San Diego

Our genomic DNA achieves cellular compaction through several hierarchical levels of organization. First, DNA wraps around certain protein spools called nucleosomes that comprise of positively charged proteins called histones. The resulting "bead-on-a-string" nucleoprotein complex folds further into a 30-nm chromatin fiber at physiological conditions in the presence of another protein called the linker histone. The thermodynamic and structural details of how histone proteins critically compact and modulate chromatin structure as well as regulate gene transcription (switch genes "on" and "off") are not well understood. In this talk, I will present the development of a new mesoscopic model of chromatin that reproduces experimental data, elucidates the physical role of each histone in chromatin folding, and proposes a new polymorphic structure of chromatin that resolves the long-standing debate between solenoid and zigzag chromatin models. Development of this model now opens up new avenues for studying the formation of higher-order structures of chromatin for studying epigenetic silencing, and the role of posttranslational modifications and variants of histone tails in gene regulation.