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

Yidai Yang; Monika Joshi; Yoh Hei Takahashi; Zhibin Ning; Qianhui Qu; Joseph S. Brunzelle; Georgios Skiniotis; Daniel Figeys; Ali Shilatifard; Jean François Couture

doi:10.1093/nar/gkz1037

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

Yidai Yang, Monika Joshi, Yoh Hei Takahashi, Zhibin Ning, Qianhui Qu, Joseph S. Brunzelle, Georgios Skiniotis, Daniel Figeys, Ali Shilatifard, Jean François Couture^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

11 Scopus citations

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.

Original language	English (US)
Pages (from-to)	421-431
Number of pages	11
Journal	Nucleic acids research
Volume	48
Issue number	1
DOIs	https://doi.org/10.1093/nar/gkz1037
State	Published - Jan 10 2020

Funding

Canadian Institutes of Health Research [MOP-136816 and PJT-148533 to Dr. Couture]; National Cancer Institute [R35CA197569 to Dr Shilatifard]; this research used resources of the Advanced Photon Source, a U.S. Department of Energy (DOE) Office of Science User Facility operated for the DOE Office of Science by Argonne National Laboratory [DE-AC02-06CH11357]; use of the LS-CAT Sector 21 was supported by the Michigan Economic Development Corporation and the Michigan Technology Tri-Corridor [085P1000817]; Dr Figeys is supported by Genome Canada and Natural Science Engineering Research Council grants. Funding for open access charge: Canadian Institutes of Health Research. Conflict of interest statement. None declared.

ASJC Scopus subject areas

Genetics

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10.1093/nar/gkz1037

Cite this

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

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.",

author = "Yidai Yang and Monika Joshi and Takahashi, {Yoh Hei} and Zhibin Ning and Qianhui Qu and Brunzelle, {Joseph S.} and Georgios Skiniotis and Daniel Figeys and Ali Shilatifard and Couture, {Jean Fran{\c c}ois}",

note = "Funding Information: Canadian Institutes of Health Research [MOP-136816 and PJT-148533 to Dr. Couture]; National Cancer Institute [R35CA197569 to Dr Shilatifard]; this research used resources of the Advanced Photon Source, a U.S. Department of Energy (DOE) Office of Science User Facility operated for the DOE Office of Science by Argonne National Laboratory [DE-AC02-06CH11357]; use of the LS-CAT Sector 21 was supported by the Michigan Economic Development Corporation and the Michigan Technology Tri-Corridor [085P1000817]; Dr Figeys is supported by Genome Canada and Natural Science Engineering Research Council grants. Funding for open access charge: Canadian Institutes of Health Research. Conflict of interest statement. None declared. Publisher Copyright: {\textcopyright} 2019 The Author(s) 2019. Published by Oxford University Press on behalf of Nucleic Acids Research.",

year = "2020",

month = jan,

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doi = "10.1093/nar/gkz1037",

language = "English (US)",

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T1 - A non-canonical monovalent zinc finger stabilizes the integration of Cfp1 into the H3K4 methyltransferase complex COMPASS

AU - Yang, Yidai

AU - Joshi, Monika

AU - Takahashi, Yoh Hei

AU - Ning, Zhibin

AU - Qu, Qianhui

AU - Brunzelle, Joseph S.

AU - Skiniotis, Georgios

AU - Figeys, Daniel

AU - Shilatifard, Ali

AU - Couture, Jean François

N1 - Funding Information: Canadian Institutes of Health Research [MOP-136816 and PJT-148533 to Dr. Couture]; National Cancer Institute [R35CA197569 to Dr Shilatifard]; this research used resources of the Advanced Photon Source, a U.S. Department of Energy (DOE) Office of Science User Facility operated for the DOE Office of Science by Argonne National Laboratory [DE-AC02-06CH11357]; use of the LS-CAT Sector 21 was supported by the Michigan Economic Development Corporation and the Michigan Technology Tri-Corridor [085P1000817]; Dr Figeys is supported by Genome Canada and Natural Science Engineering Research Council grants. Funding for open access charge: Canadian Institutes of Health Research. Conflict of interest statement. None declared. Publisher Copyright: © 2019 The Author(s) 2019. Published by Oxford University Press on behalf of Nucleic Acids Research.

PY - 2020/1/10

Y1 - 2020/1/10

N2 - 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.

AB - 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.

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JF - Nucleic acids research

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

Abstract

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Crystal structure of RbBP5 interacting domain of Cfp1

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

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ASJC Scopus subject areas

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Crystal structure of RbBP5 interacting domain of Cfp1

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