@article{84eadfb6b1db44b18eb299cbf8537e63,
title = "Nanoscale chromatin imaging and analysis platform bridges 4D chromatin organization with molecular function",
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.",
author = "Yue Li and Adam Eshein and Virk, {Ranya K.A.} and Aya Eid and Wenli Wu and Jane Frederick and David VanDerway and Scott Gladstein and Kai Huang and Shim, {Anne R.} and Anthony, {Nicholas M.} and Bauer, {Greta M.} and Xiang Zhou and Vasundhara Agrawal and Pujadas, {Emily M.} and Surbhi Jain and George Esteve and Chandler, {John E.} and Nguyen, {The Quyen} and Reiner Bleher and {de Pablo}, {Juan J.} and Igal Szleifer and Dravid, {Vinayak P.} and Almassalha, {Luay M.} and Vadim Backman",
note = "Funding Information: This work was supported by NSF grants EFMA-1830961 and EFMA-1830969, NIH grants R01CA228272 and R01CA225002, the Christina Carinato Charitable Foundation, Mark and Ingeborg Holliday, Kristin Hudson & Rob Goldman, and Ms. Susan Brice & Mr. Jordi Esteve. The ChromEM work made use of the BioCryo Facility of Northwestern University?s NUANCE Center, which has received support from the Soft and Hybrid Nanotechnology Experimental (SHyNE) Resource (NSF ECCS-1542205); the MRSEC program (NSF DMR-1720139) at the Materials Research Center; the International Institute for Nanotechnology (IIN); and the State of Illinois, through the IIN. An award of computer time was provided by the INCITE program. This research used resources of the Argonne Leadership Computing Facility, which is a DOE Office of Science User Facility supported under contract DE-AC02-06CH11357 with guidance from W. Jiang. Computational analysis of Hi-C data was supported in part through the computational resources and staff contributions provided by the Genomics Compute Cluster, which is jointly supported by the Feinberg School of Medicine, the Center for Genetic Medicine, and Feinberg?s Department of Biochemistry and Molecular Genetics, the Office of the Provost, the Office for Research, and Northwestern Information Technology. The Genomics Compute Cluster is part of Quest, Northwestern University?s high-performance computing facility, with the purpose to Publisher Copyright: Copyright {\textcopyright} 2021 The Authors, some rights reserved.",
year = "2021",
month = jan,
day = "1",
doi = "10.1126/sciadv.abe4310",
language = "English (US)",
volume = "7",
journal = "Science advances",
issn = "2375-2548",
publisher = "American Association for the Advancement of Science",
number = "1",
}