A non-canonical monovalent zinc finger stabilizes the integration of Cfp1 into the H3K4 methyltransferase complex COMPASS

Yang, Yidai, Joshi, Monika, Takahashi, Yoh Hei, Ning, Zhibin, Qu, Qianhui, Brunzelle, Joseph S., Skiniotis, Georgios, Figeys, Daniel, Shilatifard, Ali and Couture, Jean François (2020) A non-canonical monovalent zinc finger stabilizes the integration of Cfp1 into the H3K4 methyltransferase complex COMPASS. Nucleic Acids Research, 48 (1). pp. 421-431. ISSN 0305-1048

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Abstract

COMPlex ASsociating with SET1 (COMPASS) is a histone H3 Lys-4 methyltransferase that typically marks the promoter region of actively transcribed genes. COMPASS is a multi-subunit complex in which the catalytic unit, SET1, is required for H3K4 methylation. An important subunit known to regulate SET1 methyltransferase activity is the CxxC zinc finger protein 1 (Cfp1). Cfp1 binds to COMPASS and is critical to maintain high level of H3K4me3 in cells but the mechanisms underlying its stimulatory activity is poorly understood. In this study, we show that Cfp1 only modestly activates COMPASS methyltransferase activity in vitro. Binding of Cfp1 to COMPASS is in part mediated by a new type of monovalent zinc finger (ZnF). This ZnF interacts with the COMPASS's subunits RbBP5 and disruption of this interaction blunts its methyltransferase activity in cells and in vivo. Collectively, our studies reveal that a novel form of ZnF on Cfp1 enables its integration into COMPASS and contributes to epigenetic signaling.

Item Type: Article
Additional Information: Publisher Copyright: © 2019 The Author(s) 2019. Published by Oxford University Press on behalf of Nucleic Acids Research.
Uncontrolled Keywords: genetics ,/dk/atira/pure/subjectarea/asjc/1300/1311
Faculty \ School: Faculty of Medicine and Health Sciences > Norwich Medical School
UEA Research Groups: Faculty of Medicine and Health Sciences > Research Centres > Metabolic Health
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Depositing User: LivePure Connector
Date Deposited: 25 Mar 2026 17:30
Last Modified: 25 Mar 2026 17:30
URI: https://ueaeprints.uea.ac.uk/id/eprint/102578
DOI: 10.1093/nar/gkz1037

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