Dataset Information

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.

SUBMITTER: Li Y

PROVIDER: S-EPMC7775763 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature

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Nanoscale chromatin imaging and analysis platform bridges 4D chromatin organization with molecular function.

Li Yue Y Eshein Adam A Virk Ranya K A RKA Eid Aya A Wu Wenli W Frederick Jane J VanDerway David D Gladstein Scott S Huang Kai K Shim Anne R AR Anthony Nicholas M NM Bauer Greta M GM Zhou Xiang X Agrawal Vasundhara V Pujadas Emily M EM Jain Surbhi S Esteve George G Chandler John E JE Nguyen The-Quyen TQ Bleher Reiner R de Pablo Juan J JJ Szleifer Igal I Dravid Vinayak P VP Almassalha Luay M LM Backman Vadim V

Science advances 20210101 1

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, op ...[more]

PMID: 33523864

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Project description:Methodological advances in conformation capture techniques have fundamentally changed our understanding of chromatin architecture. However, the nanoscale organization of chromatin and its cell-to-cell variance are less studied. Analyzing genome-wide data from 733 human cell and tissue samples, we identified 2 prototypical regions that exhibit high or absent hypersensitivity to deoxyribonuclease I, respectively. These regulatory active or inactive regions were examined in the lymphoblast cell line K562 by using high-throughput super-resolution microscopy. In both regions, we systematically measured the physical distance of 2 fluorescence in situ hybridization spots spaced by only 5 kb of DNA. Unexpectedly, the resulting distance distributions range from very compact to almost elongated configurations of more than 200-nm length for both the active and inactive regions. Monte Carlo simulations of a coarse-grained model of these chromatin regions based on published data of nucleosome occupancy in K562 cells were performed to understand the underlying mechanisms. There was no parameter set for the simulation model that can explain the microscopically measured distance distributions. Obviously, the chromatin state given by the strength of internucleosomal interaction, nucleosome occupancy, or amount of histone H1 differs from cell to cell, which results in the observed broad distance distributions. This large variability was not expected, especially in inactive regions. The results for the mechanisms for different distance distributions on this scale are important for understanding the contacts that mediate gene regulation. Microscopic measurements show that the inactive region investigated here is expected to be embedded in a more compact chromatin environment. The simulation results of this region require an increase in the strength of internucleosomal interactions. It may be speculated that the higher density of chromatin is caused by the increased internucleosomal interaction strength.

Dataset Information

Nanoscale chromatin imaging and analysis platform bridges 4D chromatin organization with molecular function.

Publications

Nanoscale chromatin imaging and analysis platform bridges 4D chromatin organization with molecular function.

Similar Datasets

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