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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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