Journal
SCIENCE ADVANCES
Volume 7, Issue 1, Pages -Publisher
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/sciadv.abe4310
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Funding
- NSF [EFMA-1830961, EFMA-1830969]
- NIH [R01CA228272, R01CA225002]
- Christina Carinato Charitable Foundation
- Soft and Hybrid Nanotechnology Experimental (SHyNE) Resource [NSF ECCS-1542205]
- MRSEC program at the Materials Research Center [NSF DMR-1720139]
- International Institute for Nanotechnology (IIN)
- State of Illinois, through the IIN
- INCITE program
- DOE Office of Science User Facility [DE-AC02-06CH11357]
- Feinberg School of Medicine
- Center for Genetic Medicine, and Feinberg's Department of Biochemistry and Molecular Genetics
- Office of the Provost
- Office for Research
- Northwestern Information Technology
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The study introduces a multi-technique nanoscale chromatin imaging and analysis platform, revealing spatially separable packing domains of chromatin with a complex bidirectional relationship between chromatin packing behavior and active gene transcription. Furthermore, properties of these domains are correlated among progenitor and progeny cells across cell division.
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.
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