Targeted DNA methylation in vivo using an engineered dCas9-MQ1 fusion protein
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 neurodegenera...
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Published in | Nature communications Vol. 8; no. 1; p. 16026 |
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Main Authors | , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
London
Nature Publishing Group UK
11.07.2017
Nature Publishing Group Nature Portfolio |
Subjects | |
Online Access | Get full text |
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Summary: | 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.
Understanding how DNA methylation regulates gene expression requires the capacity to deploy it to regions of interest. The authors generate a highly rapid and locus-specific CpG methylation tool by fusing dCas9 to MQ1 DNA methyltransferase and show efficacy at multiple sites
in vitro
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in vivo
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Bibliography: | ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Undefined-1 ObjectType-Feature-3 content type line 23 These authors contributed equally to this work. Present address: Center for Epigenetics, Van Andel Research Institution, Grand Rapids, Michigan 49503, USA |
ISSN: | 2041-1723 2041-1723 |
DOI: | 10.1038/ncomms16026 |