PRC1 catalytic activity is central to Polycomb system function
The Polycomb repressive system is an essential chromatin-based regulator of gene expression. Despite being extensively studied, how the Polycomb system selects its target genes is poorly understood, and whether its histone-modifying activities are required for transcriptional repression remains cont...
| Main Authors: | , , , , , |
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| Format: | Journal article |
| Language: | English |
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Elsevier
2019
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| _version_ | 1826304267935285248 |
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| author | Blackledge, NP Fursova, NA Kelley, JR Huseyin, MK Feldmann, A Klose, RJ |
| author_facet | Blackledge, NP Fursova, NA Kelley, JR Huseyin, MK Feldmann, A Klose, RJ |
| author_sort | Blackledge, NP |
| collection | OXFORD |
| description | The Polycomb repressive system is an essential chromatin-based regulator of gene expression. Despite being extensively studied, how the Polycomb system selects its target genes is poorly understood, and whether its histone-modifying activities are required for transcriptional repression remains controversial. Here, we directly test the requirement for PRC1 catalytic activity in Polycomb system function. To achieve this, we develop a conditional mutation system in embryonic stem cells that completely removes PRC1 catalytic activity. Using this system, we demonstrate that catalysis by PRC1 drives Polycomb chromatin domain formation and long-range chromatin interactions. Furthermore, we show that variant PRC1 complexes with DNA-binding activities occupy target sites independently of PRC1 catalytic activity, providing a putative mechanism for Polycomb target site selection. Finally, we discover that Polycomb-mediated gene repression requires PRC1 catalytic activity. Together these discoveries provide compelling evidence that PRC1 catalysis is central to Polycomb system function and gene regulation. |
| first_indexed | 2024-03-07T06:15:14Z |
| format | Journal article |
| id | oxford-uuid:f0daa1fa-94da-4da9-8496-5cf543a9134b |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T06:15:14Z |
| publishDate | 2019 |
| publisher | Elsevier |
| record_format | dspace |
| spelling | oxford-uuid:f0daa1fa-94da-4da9-8496-5cf543a9134b2022-03-27T11:51:24ZPRC1 catalytic activity is central to Polycomb system functionJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:f0daa1fa-94da-4da9-8496-5cf543a9134bEnglishSymplectic Elements at OxfordElsevier2019Blackledge, NPFursova, NAKelley, JRHuseyin, MKFeldmann, AKlose, RJThe Polycomb repressive system is an essential chromatin-based regulator of gene expression. Despite being extensively studied, how the Polycomb system selects its target genes is poorly understood, and whether its histone-modifying activities are required for transcriptional repression remains controversial. Here, we directly test the requirement for PRC1 catalytic activity in Polycomb system function. To achieve this, we develop a conditional mutation system in embryonic stem cells that completely removes PRC1 catalytic activity. Using this system, we demonstrate that catalysis by PRC1 drives Polycomb chromatin domain formation and long-range chromatin interactions. Furthermore, we show that variant PRC1 complexes with DNA-binding activities occupy target sites independently of PRC1 catalytic activity, providing a putative mechanism for Polycomb target site selection. Finally, we discover that Polycomb-mediated gene repression requires PRC1 catalytic activity. Together these discoveries provide compelling evidence that PRC1 catalysis is central to Polycomb system function and gene regulation. |
| spellingShingle | Blackledge, NP Fursova, NA Kelley, JR Huseyin, MK Feldmann, A Klose, RJ PRC1 catalytic activity is central to Polycomb system function |
| title | PRC1 catalytic activity is central to Polycomb system function |
| title_full | PRC1 catalytic activity is central to Polycomb system function |
| title_fullStr | PRC1 catalytic activity is central to Polycomb system function |
| title_full_unstemmed | PRC1 catalytic activity is central to Polycomb system function |
| title_short | PRC1 catalytic activity is central to Polycomb system function |
| title_sort | prc1 catalytic activity is central to polycomb system function |
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