Chemistry Seminar: Dr. Xingcheng Lin

The Department of Chemistry in the College of Arts and Sciences is pleased to welcome Dr. Xingcheng Lin, a Postdoctoral Associate at MIT.

The seminar will be held on Zoom. Please email chemistry@syr.edu for Zoom info.

Title: Near-atomistic Modeling of Chromatin — Breaking Size Limit to Uncover Mechanistic Insights

Abstract

Three-dimensional chromatin organization lays the foundation for biological processes involving gene expression and epigenetic regulation. Nevertheless, it is unclear how chromatin is structured at the fundamental level. There is a heated debate over the existence of chromatin fibril structure and its regulation by multiple epigenetic regulators. Controversy also remains on the sol-gel properties of chromatin subject to different environmental conditions. Here, building upon our recently implemented near-atomistic chromatin model, we leveraged computational advances to study structural details of large chromatin systems. Our study with a tetranucleosome, the fundamental unit of chromatin, captures multiple irregular chromatin structures that emerge as intermediates of two chromatin folding pathways. Our further study with a dodecameric nucleosomal array reproduces

the force-extension curve measured by magnetic tweezers. The simulation also reveals a more complicated folding landscape of chromatin under tension than a two-state transition: Whereas the shearing motion of compact chromatin under lower tension constitutes the “linear” response regime, a mixture of trinucleosome and tetranucleosome clutches appears as tension increases, leading to an extended nucleosomal array represented as the “plateau” regime on the force-extension curve. Additional simulations with multiple chromatins reveal a stable interdigitated configuration, thereby suggesting a mechanism initiating the sol-gel transition of chromatin. Finally, we show that Polycomb repressive complex 2 (PRC2), a critical epigenetic modification enzyme, can cooperatively loop DNA via allosteric communication and can bridge non-adjacent nucleosomes to spread histone modifications. Our integrated work demonstrates the usefulness of the near-atomistic model in reconciling the stability of different chromatin conformations under in vitro and in vivo environments and revealing mechanistic insights on the impact of epigenetic regulators on genome organization.