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Structure of nucleosome-bound DNA methyltransferases DNMT3A and DNMT3B

Author

Listed:
  • Ting-Hai Xu

    (Van Andel Institute
    Van Andel Institute)

  • Minmin Liu

    (Van Andel Institute)

  • X. Edward Zhou

    (Van Andel Institute)

  • Gangning Liang

    (University of Southern California, Los Angeles)

  • Gongpu Zhao

    (Van Andel Institute)

  • H. Eric Xu

    (Chinese Academy of Sciences)

  • Karsten Melcher

    (Van Andel Institute)

  • Peter A. Jones

    (Van Andel Institute)

Abstract

CpG methylation by de novo DNA methyltransferases (DNMTs) 3A and 3B is essential for mammalian development and differentiation and is frequently dysregulated in cancer1. These two DNMTs preferentially bind to nucleosomes, yet cannot methylate the DNA wrapped around the nucleosome core2, and they favour the methylation of linker DNA at positioned nucleosomes3,4. Here we present the cryo-electron microscopy structure of a ternary complex of catalytically competent DNMT3A2, the catalytically inactive accessory subunit DNMT3B3 and a nucleosome core particle flanked by linker DNA. The catalytic-like domain of the accessory DNMT3B3 binds to the acidic patch of the nucleosome core, which orients the binding of DNMT3A2 to the linker DNA. The steric constraints of this arrangement suggest that nucleosomal DNA must be moved relative to the nucleosome core for de novo methylation to occur.

Suggested Citation

  • Ting-Hai Xu & Minmin Liu & X. Edward Zhou & Gangning Liang & Gongpu Zhao & H. Eric Xu & Karsten Melcher & Peter A. Jones, 2020. "Structure of nucleosome-bound DNA methyltransferases DNMT3A and DNMT3B," Nature, Nature, vol. 586(7827), pages 151-155, October.
    • Handle: RePEc:nat:nature:v:586:y:2020:i:7827:d:10.1038_s41586-020-2747-1
    DOI: 10.1038/s41586-020-2747-1
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    Cited by:

    1. Jiuwei Lu & Yiran Guo & Jiekai Yin & Jianbin Chen & Yinsheng Wang & Gang Greg Wang & Jikui Song, 2024. "Structure-guided functional suppression of AML-associated DNMT3A hotspot mutations," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    2. Xinyi Chen & Yiran Guo & Ting Zhao & Jiuwei Lu & Jian Fang & Yinsheng Wang & Gang Greg Wang & Jikui Song, 2024. "Structural basis for the H2AK119ub1-specific DNMT3A-nucleosome interaction," Nature Communications, Nature, vol. 15(1), pages 1-16, December.

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