Nanoscale chromatin imaging and analysis platform bridges 4D chromatin organization with molecular function
Yue Li, Adam Eshein, Ranya Virk, Aya Eid, Wenli Wu, Jane Frederick, David VanDerway, Scott Gladstein, Kai Huang, Anne R. Shim, Nicholas M. Anthony, Greta M. Bauer, Xiang Zhou, Vasundhara Agrawal, Emily M. Pujadas-Liwag, Surbhi Jain, George Esteve, John E. Chandler, The‐Quyen Nguyen, Reiner Bleher, Juan Pablo, Igal Szleifer, Vinayak P. Dravid, Luay M. Almassalha, Vadim Backman
Abstract
Extending across multiple length scales, dynamic chromatin structure is linked to transcription through the regulation of genome organization. However, no individual technique can fully elucidate this structure and its relation to molecular function at all length and time scales at both a single-cell level and a population level. Here, we present a multitechnique nanoscale chromatin imaging and analysis (nano-ChIA) platform that consolidates electron tomography of the primary chromatin fiber, optical super-resolution imaging of transcription processes, and label-free nano-sensing of chromatin packing and its dynamics in live cells. Using nano-ChIA, we observed that chromatin is localized into spatially separable packing domains, with an average diameter of around 200 nanometers, sub-megabase genomic size, and an internal fractal structure. The chromatin packing behavior of these domains exhibits a complex bidirectional relationship with active gene transcription. Furthermore, we found that properties of PDs are correlated among progenitor and progeny cells across cell division.