Soya Shinkai (RIKEN): Fluctuation of the 3D Genome from Modeling and Experiments
Genomic DNA is hierarchically folded and compacted in the micrometer-sized cell nucleus, and its three-dimensional (3D) organization plays a crucial role in gene regulation. This architecture is inherently dynamic, continuously fluctuating over time. Understanding this “fluctuation” is essential for elucidating the relationship between genome structure and its functions.
In fixed cell populations, such structural fluctuations manifest as cell-to-cell variability. With the advent of Hi-C technology, it has become possible to indirectly infer 3D genome structures using next-generation sequencing. On the other hand, live-cell imaging enables the direct observation of real-time fluctuations in the positions and dynamics of specific genomic loci and chromatin segments.
To bridge these complementary approaches, we have developed a theoretical framework and analysis method called PHi-C, which integrates Hi-C and chromatin dynamics data. PHi-C employs a polymer model with linear all-to-all pairwise interactions, from which interaction parameters can be accurately inferred from Hi-C data through the PHi-C optimization algorithm. This allows for the prediction of time-resolved fluctuations at individual genomic regions, enabling integration with live-cell imaging data. As a result, we can construct a unified physical model that simultaneously reproduces both the 3D structure and dynamic behavior of chromatin in the nucleus.
More recently, we have shown that the motion of a single monomer within this polymer model, when compared with chromatin tracking experiments, rigorously follows a generalized Langevin equation derived from the projection method.
In this talk, I will introduce our integrated modeling framework and highlight key findings on the dynamic nature of the 3D genome revealed through a combination of experimental data and computational modeling.
Zoom Information:
https://us02web.zoom.us/j/2022111100
(Meeting code: 2022111100 Password: skcm2)