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

Yong Lei, Xiaotian Zhang, Jianzhong Su, Mira Jeong, Michael C. Gundry, Yung-Hsin Huang, Yubin Zhou, Wei Li and Margaret A. Goodell ()
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Yong Lei: Center for Cell and Gene Therapy, Baylor College of Medicine
Xiaotian Zhang: Center for Cell and Gene Therapy, Baylor College of Medicine
Jianzhong Su: Baylor College of Medicine
Mira Jeong: Center for Cell and Gene Therapy, Baylor College of Medicine
Michael C. Gundry: Center for Cell and Gene Therapy, Baylor College of Medicine
Yung-Hsin Huang: Stem Cells and Regenerative Medicine Center, 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

Nature Communications, 2017, vol. 8, issue 1, 1-10

Abstract: 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.

Date: 2017
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_ncomms16026

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DOI: 10.1038/ncomms16026

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