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

Research output: Contribution to journalArticle

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 languageEnglish (US)
Pages (from-to)421-431
Number of pages11
JournalNucleic acids research
Volume48
Issue number1
DOIs
StatePublished - Jan 10 2020

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Zinc Fingers
Methyltransferases
Proteins
Genetic Promoter Regions
Epigenomics
Histones
Methylation
Genes

ASJC Scopus subject areas

  • Genetics

Cite this

Yang, Yidai ; Joshi, Monika ; Takahashi, Yoh Hei ; Ning, Zhibin ; Qu, Qianhui ; Brunzelle, Joseph S. ; Skiniotis, Georgios ; Figeys, Daniel ; Shilatifard, Ali ; Couture, Jean François. / A non-canonical monovalent zinc finger stabilizes the integration of Cfp1 into the H3K4 methyltransferase complex COMPASS. In: Nucleic acids research. 2020 ; Vol. 48, No. 1. pp. 421-431.
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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; Couture, Jean François.

In: Nucleic acids research, Vol. 48, No. 1, 10.01.2020, p. 421-431.

Research output: Contribution to journalArticle

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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

PY - 2020/1/10

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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.

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