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CK2-mediated phosphorylation of SUZ12 promotes PRC2 function by stabilizing enzyme active site

Author

Listed:
  • Lihu Gong

    (University of Texas Southwestern Medical Center)

  • Xiuli Liu

    (University of Texas Southwestern Medical Center)

  • Lianying Jiao

    (University of Texas Southwestern Medical Center
    Xi’an Jiaotong University Health Science Center)

  • Xin Yang

    (University of Texas Southwestern Medical Center)

  • Andrew Lemoff

    (University of Texas Southwestern Medical Center)

  • Xin Liu

    (University of Texas Southwestern Medical Center)

Abstract

Polycomb repressive complex 2 (PRC2) plays a key role in maintaining cell identity during differentiation. Methyltransferase activity of PRC2 on histone H3 lysine 27 is regulated by diverse cellular mechanisms, including posttranslational modification. Here, we report a unique phosphorylation-dependent mechanism stimulating PRC2 enzymatic activity. Residue S583 of SUZ12 is phosphorylated by casein kinase 2 (CK2) in cells. A crystal structure captures phosphorylation in action: the flexible phosphorylation-dependent stimulation loop harboring S583 becomes engaged with the catalytic SET domain through a phosphoserine-centered interaction network, stabilizing the enzyme active site and in particular S-adenosyl-methionine (SAM)-binding pocket. CK2-mediated S583 phosphorylation promotes catalysis by enhancing PRC2 binding to SAM and nucleosomal substrates and facilitates reporter gene repression. Loss of S583 phosphorylation impedes PRC2 recruitment and H3K27me3 deposition in pluripotent mESCs and compromises the ability of PRC2 to maintain differentiated cell identity.

Suggested Citation

  • Lihu Gong & Xiuli Liu & Lianying Jiao & Xin Yang & Andrew Lemoff & Xin Liu, 2022. "CK2-mediated phosphorylation of SUZ12 promotes PRC2 function by stabilizing enzyme active site," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-34431-1
    DOI: 10.1038/s41467-022-34431-1
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    1. Zhonghua Gao & Pedro Lee & James M. Stafford & Melanie von Schimmelmann & Anne Schaefer & Danny Reinberg, 2014. "An AUTS2–Polycomb complex activates gene expression in the CNS," Nature, Nature, vol. 516(7531), pages 349-354, December.
    2. Roberta Ragazzini & Raquel Pérez-Palacios & Irem H. Baymaz & Seynabou Diop & Katia Ancelin & Dina Zielinski & Audrey Michaud & Maëlle Givelet & Mate Borsos & Setareh Aflaki & Patricia Legoix & Pascal , 2019. "EZHIP constrains Polycomb Repressive Complex 2 activity in germ cells," Nature Communications, Nature, vol. 10(1), pages 1-18, December.
    3. Neil Justin & Ying Zhang & Cataldo Tarricone & Stephen R. Martin & Shuyang Chen & Elizabeth Underwood & Valeria De Marco & Lesley F. Haire & Philip A. Walker & Danny Reinberg & Jon R. Wilson & Steven , 2016. "Structural basis of oncogenic histone H3K27M inhibition of human polycomb repressive complex 2," Nature Communications, Nature, vol. 7(1), pages 1-11, September.
    4. Qi-Long Ying & Jason Wray & Jennifer Nichols & Laura Batlle-Morera & Bradley Doble & James Woodgett & Philip Cohen & Austin Smith, 2008. "The ground state of embryonic stem cell self-renewal," Nature, Nature, vol. 453(7194), pages 519-523, May.
    5. Raphaël Margueron & Danny Reinberg, 2011. "The Polycomb complex PRC2 and its mark in life," Nature, Nature, vol. 469(7330), pages 343-349, January.
    6. Siddhant U. Jain & Truman J. Do & Peder J. Lund & Andrew Q. Rashoff & Katharine L. Diehl & Marcin Cieslik & Andrea Bajic & Nikoleta Juretic & Shriya Deshmukh & Sriram Venneti & Tom W. Muir & Benjamin , 2019. "PFA ependymoma-associated protein EZHIP inhibits PRC2 activity through a H3 K27M-like mechanism," Nature Communications, Nature, vol. 10(1), pages 1-14, December.
    7. Raphael Margueron & Neil Justin & Katsuhito Ohno & Miriam L. Sharpe & Jinsook Son & William J. Drury III & Philipp Voigt & Stephen R. Martin & William R. Taylor & Valeria De Marco & Vincenzo Pirrotta , 2009. "Role of the polycomb protein EED in the propagation of repressive histone marks," Nature, Nature, vol. 461(7265), pages 762-767, October.
    8. Alexei Brooun & Ketan S. Gajiwala & Ya-Li Deng & Wei Liu & Ben Bolaños & Patrick Bingham & You-Ai He & Wade Diehl & Nicole Grable & Pei-Pei Kung & Scott Sutton & Karen A. Maegley & Xiu Yu & Al E. Stew, 2016. "Polycomb repressive complex 2 structure with inhibitor reveals a mechanism of activation and drug resistance," Nature Communications, Nature, vol. 7(1), pages 1-12, September.
    9. Sarah Cooper & Anne Grijzenhout & Elizabeth Underwood & Katia Ancelin & Tianyi Zhang & Tatyana B. Nesterova & Burcu Anil-Kirmizitas & Andrew Bassett & Susanne M. Kooistra & Karl Agger & Kristian Helin, 2016. "Jarid2 binds mono-ubiquitylated H2A lysine 119 to mediate crosstalk between Polycomb complexes PRC1 and PRC2," Nature Communications, Nature, vol. 7(1), pages 1-8, December.
    Full references (including those not matched with items on IDEAS)

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