PRC1 Catalytic Activity Is Central to Polycomb System Function.
Autor: | Blackledge NP; Department of Biochemistry, University of Oxford, South Parks Rd., Oxford OX1 3QU, UK., Fursova NA; Department of Biochemistry, University of Oxford, South Parks Rd., Oxford OX1 3QU, UK., Kelley JR; Department of Biochemistry, University of Oxford, South Parks Rd., Oxford OX1 3QU, UK., Huseyin MK; Department of Biochemistry, University of Oxford, South Parks Rd., Oxford OX1 3QU, UK., Feldmann A; Department of Biochemistry, University of Oxford, South Parks Rd., Oxford OX1 3QU, UK., Klose RJ; Department of Biochemistry, University of Oxford, South Parks Rd., Oxford OX1 3QU, UK. Electronic address: rob.klose@bioch.ox.ac.uk. |
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Jazyk: | angličtina |
Zdroj: | Molecular cell [Mol Cell] 2020 Feb 20; Vol. 77 (4), pp. 857-874.e9. Date of Electronic Publication: 2019 Dec 27. |
DOI: | 10.1016/j.molcel.2019.12.001 |
Abstrakt: | 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. Competing Interests: Declaration of Interests The authors declare no competing interests. (Copyright © 2019 The Author(s). Published by Elsevier Inc. All rights reserved.) |
Databáze: | MEDLINE |
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