Live-cell single particle tracking of PRC1 reveals a highly dynamic system with low target site occupancy
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, w...
| Main Authors: | , |
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| Format: | Journal article |
| Language: | English |
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Springer Nature
2021
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| _version_ | 1826276124554952704 |
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| author | Klose, RJ Huseyin, M |
| author_facet | Klose, RJ Huseyin, M |
| author_sort | Klose, RJ |
| collection | OXFORD |
| description | 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. |
| first_indexed | 2024-03-06T23:09:16Z |
| format | Journal article |
| id | oxford-uuid:64e74c0a-893c-4039-b1ce-f9e79e6c1b81 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T23:09:16Z |
| publishDate | 2021 |
| publisher | Springer Nature |
| record_format | dspace |
| spelling | oxford-uuid:64e74c0a-893c-4039-b1ce-f9e79e6c1b812022-03-26T18:22:03ZLive-cell single particle tracking of PRC1 reveals a highly dynamic system with low target site occupancyJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:64e74c0a-893c-4039-b1ce-f9e79e6c1b81EnglishSymplectic ElementsSpringer Nature2021Klose, RJHuseyin, MPolycomb 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. |
| spellingShingle | Klose, RJ Huseyin, M Live-cell single particle tracking of PRC1 reveals a highly dynamic system with low target site occupancy |
| title | Live-cell single particle tracking of PRC1 reveals a highly dynamic system with low target site occupancy |
| title_full | Live-cell single particle tracking of PRC1 reveals a highly dynamic system with low target site occupancy |
| title_fullStr | Live-cell single particle tracking of PRC1 reveals a highly dynamic system with low target site occupancy |
| title_full_unstemmed | Live-cell single particle tracking of PRC1 reveals a highly dynamic system with low target site occupancy |
| title_short | Live-cell single particle tracking of PRC1 reveals a highly dynamic system with low target site occupancy |
| title_sort | live cell single particle tracking of prc1 reveals a highly dynamic system with low target site occupancy |
| work_keys_str_mv | AT kloserj livecellsingleparticletrackingofprc1revealsahighlydynamicsystemwithlowtargetsiteoccupancy AT huseyinm livecellsingleparticletrackingofprc1revealsahighlydynamicsystemwithlowtargetsiteoccupancy |