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

Yue Li; Adam Eshein; Ranya K.A. 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; Surbhi Jain; George Esteve; John E. Chandler; The Quyen Nguyen; Reiner Bleher; Juan J. de Pablo; Igal Szleifer; Vinayak P. Dravid; Luay M. Almassalha; Vadim Backman

doi:10.1126/sciadv.abe4310

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

Yue Li, Adam Eshein, Ranya K.A. 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, Surbhi Jain, George Esteve, John E. Chandler, The Quyen Nguyen, Reiner BleherJuan J. de Pablo, Igal Szleifer, Vinayak P. Dravid, Luay M. Almassalha, Vadim Backman^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

38 Scopus citations

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.

Original language	English (US)
Article number	eabe4310
Journal	Science Advances
Volume	7
Issue number	1
DOIs	https://doi.org/10.1126/sciadv.abe4310
State	Published - Jan 1 2021

Funding

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\u2019s 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\u2019s 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\u2019s high-performance computing facility, with the purpose to

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Li, Y., Eshein, A., Virk, R. K. A., Eid, A., Wu, W., Frederick, J., VanDerway, D., Gladstein, S., Huang, K., Shim, A. R., Anthony, N. M., Bauer, G. M., Zhou, X., Agrawal, V., Pujadas, E. M., Jain, S., Esteve, G., Chandler, J. E., Nguyen, T. Q., ... Backman, V. (2021). Nanoscale chromatin imaging and analysis platform bridges 4D chromatin organization with molecular function. Science Advances, 7(1), Article eabe4310. https://doi.org/10.1126/sciadv.abe4310

@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{\textquoteright}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{\textquoteright}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{\textquoteright}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",

}

Li, Y, Eshein, A, Virk, RKA, Eid, A, Wu, W, Frederick, J, VanDerway, D, Gladstein, S, Huang, K, Shim, AR, Anthony, NM, Bauer, GM, Zhou, X, Agrawal, V, Pujadas, EM, Jain, S, Esteve, G, Chandler, JE, Nguyen, TQ, Bleher, R, de Pablo, JJ, Szleifer, I , Dravid, VP, Almassalha, LM & Backman, V 2021, 'Nanoscale chromatin imaging and analysis platform bridges 4D chromatin organization with molecular function', Science Advances, vol. 7, no. 1, eabe4310. https://doi.org/10.1126/sciadv.abe4310

TY - JOUR

T1 - Nanoscale chromatin imaging and analysis platform bridges 4D chromatin organization with molecular function

AU - Li, Yue

AU - Eshein, Adam

AU - Virk, Ranya K.A.

AU - Eid, Aya

AU - Wu, Wenli

AU - Frederick, Jane

AU - VanDerway, David

AU - Gladstein, Scott

AU - Huang, Kai

AU - Shim, Anne R.

AU - Anthony, Nicholas M.

AU - Bauer, Greta M.

AU - Zhou, Xiang

AU - Agrawal, Vasundhara

AU - Pujadas, Emily M.

AU - Jain, Surbhi

AU - Esteve, George

AU - Chandler, John E.

AU - Nguyen, The Quyen

AU - Bleher, Reiner

AU - de Pablo, Juan J.

AU - Szleifer, Igal

AU - Dravid, Vinayak P.

AU - Almassalha, Luay M.

AU - Backman, Vadim

N1 - 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 © 2021 The Authors, some rights reserved.

PY - 2021/1/1

Y1 - 2021/1/1

N2 - 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.

AB - 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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UR - http://www.scopus.com/inward/citedby.url?scp=85098714856&partnerID=8YFLogxK

U2 - 10.1126/sciadv.abe4310

DO - 10.1126/sciadv.abe4310

M3 - Article

C2 - 33523864

AN - SCOPUS:85098714856

SN - 2375-2548

VL - 7

JO - Science Advances

JF - Science Advances

IS - 1

M1 - eabe4310

ER -

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

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