Live-cell single particle tracking of PRC1 reveals a highly dynamic system with low target site occupancy
Open accessPublished version of a preprint
Abstract
Polycomb repressive complex 1 (PRC1) is an essential chromatin-based repressor of gene transcription. 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 observe 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 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, suggesting that chromatin modification, as opposed to PRC1 complex occupancy, is central to gene repression.
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- Authors
- Huseyin, M. K., & Klose, R. J.
- Affiliations
- University of Oxford (GB)
- Corresponding author
- Klose, Robert J.
- Venue
- Nature Communications
- Published
- 2021-02-09
- Volume
- 12
- Issue
- 1
- Pages
- 887-887
- ISSN
- 2041-1723 (ISSN-L)
- PMC
- PMC7873255
- OpenAlex
- W3128025522
- Cited by
- 69
- References
- 7
- Citations by year
- 2026: 12 · 2025: 8 · 2024: 13 · 2023: 7 · 2022: 16 · 2021: 12 · 2020: 1
- FWCI
- 3.77
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- 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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