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Targeted DNA methylation in vivo using an engineered dCas9-MQ1 fusion protein

Author

Listed:
  • Yong Lei

    (Center for Cell and Gene Therapy, Baylor College of Medicine
    Stem Cells and Regenerative Medicine Center, Baylor College of Medicine)

  • Xiaotian Zhang

    (Center for Cell and Gene Therapy, Baylor College of Medicine
    Stem Cells and Regenerative Medicine Center, Baylor College of Medicine
    Present address: Center for Epigenetics, Van Andel Research Institution, Grand Rapids, Michigan 49503, USA)

  • Jianzhong Su

    (Baylor College of Medicine)

  • Mira Jeong

    (Center for Cell and Gene Therapy, Baylor College of Medicine
    Stem Cells and Regenerative Medicine Center, Baylor College of Medicine)

  • Michael C. Gundry

    (Center for Cell and Gene Therapy, Baylor College of Medicine
    Stem Cells and Regenerative Medicine Center, Baylor College of Medicine)

  • Yung-Hsin Huang

    (Stem Cells and Regenerative Medicine Center, Baylor College of Medicine
    Baylor College of Medicine)

  • Yubin Zhou

    (Center for Translational Cancer Research, Institute of Biosciences and Technology, College of Medicine, Texas A&M University)

  • Wei Li

    (Stem Cells and Regenerative Medicine Center, Baylor College of Medicine)

  • Margaret A. Goodell

    (Center for Cell and Gene Therapy, Baylor College of Medicine
    Stem Cells and Regenerative Medicine Center, Baylor College of Medicine
    Baylor College of Medicine)

Abstract

Comprehensive studies have shown that DNA methylation plays vital roles in both loss of pluripotency and governance of the transcriptome during embryogenesis and subsequent developmental processes. Aberrant DNA methylation patterns have been widely observed in tumorigenesis, ageing and neurodegenerative diseases, highlighting the importance of a systematic understanding of DNA methylation and the dynamic changes of methylomes during disease onset and progression. Here we describe a facile and convenient approach for efficient targeted DNA methylation by fusing inactive Cas9 (dCas9) with an engineered prokaryotic DNA methyltransferase MQ1. Our study presents a rapid and efficient strategy to achieve locus-specific cytosine modifications in the genome without obvious impact on global methylation in 24 h. Finally, we demonstrate our tool can induce targeted CpG methylation in mice by zygote microinjection, thereby demonstrating its potential utility in early development.

Suggested Citation

  • Yong Lei & Xiaotian Zhang & Jianzhong Su & Mira Jeong & Michael C. Gundry & Yung-Hsin Huang & Yubin Zhou & Wei Li & Margaret A. Goodell, 2017. "Targeted DNA methylation in vivo using an engineered dCas9-MQ1 fusion protein," Nature Communications, Nature, vol. 8(1), pages 1-10, December.
    • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_ncomms16026
    DOI: 10.1038/ncomms16026
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    Cited by:

    1. Jie Liu & Xuehua Zhong, 2024. "Epiallelic variation of non-coding RNA genes and their phenotypic consequences," Nature Communications, Nature, vol. 15(1), pages 1-11, December.
    2. William Senapedis & Kayleigh M. Gallagher & Elmer Figueroa & Jeremiah D. Farelli & Robert Lyng & J. Graeme Hodgson & Charles W. O’Donnell & Joseph V. Newman & Madison Pacaro & Stephen K. Siecinski & J, 2024. "Targeted transcriptional downregulation of MYC using epigenomic controllers demonstrates antitumor activity in hepatocellular carcinoma models," Nature Communications, Nature, vol. 15(1), pages 1-17, December.

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