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PreprintCited by 69Epigenetics and DNA MethylationGenomics and Chromatin DynamicsChromatin Remodeling and Cancer

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Live-cell single particle tracking of PRC1 reveals a highly dynamic system with low target site occupancy

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Huseyin, Miles K., Klose, Robert J.·2020·Nature Communications
DOI 10.1101/2020.04.25.061358PMC PMC7873255

Preprint — published as 10.1038/s41467-021-21130-6 · Paper page

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Abstract

Polycomb repressive complex 1 (PRC1) is an essential chromatin-based repressor of gene transcription. However, how PRC1 engages with chromatin to identify its target genes and achieve gene repression remains poorly defined, representing a major hurdle to our understanding of Polycomb system function. Here we use genome engineering and single particle tracking to dissect how PRC1 binds to chromatin in live mouse embryonic stem cells. We reveal that PRC1 is highly dynamic, with only a small fraction stably interacting with chromatin. By integrating subunit-specific dynamics, chromatin binding, and abundance measurements, we discover that PRC1 exhibits surprisingly low occupancy at target sites. Furthermore, we employ perturbation approaches to uncover how specific components of PRC1 define its kinetics and chromatin binding. Together, these discoveries provide a quantitative understanding of chromatin binding by PRC1 in live cells, and suggests that chromatin modification, as opposed to PRC1 complex occupancy, is central to gene repression.

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Metadata

Authors
Huseyin, M. K., & Klose, R. J.
Affiliations
University of Oxford (GB)
Corresponding author
Klose, Robert J.
ORCID
Venue
Nature Communications
Publisher
openRxiv
Published
2020-04-25
Volume
12
Issue
1
Pages
887-887
ISSN
2041-1723 (ISSN-L)
DOI
10.1101/2020.04.25.061358
PMC
PMC7873255
OpenAlex
W3128025522
Cited by
69
References
1
Citations by year
2026: 12 · 2025: 8 · 2024: 13 · 2023: 7 · 2022: 16 · 2021: 12 · 2020: 1
FWCI
3.76
Type
journal article
Language
en
Open access
Licence
Locations
  • Nature Communications (publishedVersion, cc-by)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • RePEc: Research Papers in Economics (submittedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • Wellcome Trust (091911/B/10/Z and 107457/Z/15/Z, 107457/Z/15/Z, 107457, Z/17/Z, 681440, 109102, 109102/Z/15/Z, 209400/Z/17/Z, 091911/B/10/Z, /Z/15/Z, 091911, 209400)
  • Lister Institute of Preventive Medicine
  • H2020 European Research Council (681440)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Chromatin Remodeling and Cancer
Keywords
PRC1, chromatin binding, gene repression, chromatin modification, protein dynamics, mouse embryonic stem cells, live-cell imaging, single-particle tracking, genome editing
MeSH terms
Mouse Embryonic Stem Cells, Protein Domains, Single Molecule Imaging, Animals, Binding Sites, Chromatin, Histones, Protein Binding, Protein Subunits, Mice, Polycomb Repressive Complex 1, Polycomb Repressive Complex 2

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