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Targeted DNA methylation in vivo using an engineered dCas9-MQ1 fusion protein.
Lei, Yong; Zhang, Xiaotian; Su, Jianzhong; Jeong, Mira; Gundry, Michael C; Huang, Yung-Hsin; Zhou, Yubin; Li, Wei; Goodell, Margaret A.
Afiliación
  • Lei Y; Department of Molecular and Human Genetics, Center for Cell and Gene Therapy, Baylor College of Medicine, Houston, Texas 77030, USA.
  • Zhang X; Stem Cells and Regenerative Medicine Center, Baylor College of Medicine, Houston, Texas 77030, USA.
  • Su J; Department of Molecular and Human Genetics, Center for Cell and Gene Therapy, Baylor College of Medicine, Houston, Texas 77030, USA.
  • Jeong M; Stem Cells and Regenerative Medicine Center, Baylor College of Medicine, Houston, Texas 77030, USA.
  • Gundry MC; Dan L. Duncan Cancer Center and Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas 77030, USA.
  • Huang YH; Department of Molecular and Human Genetics, Center for Cell and Gene Therapy, Baylor College of Medicine, Houston, Texas 77030, USA.
  • Zhou Y; Stem Cells and Regenerative Medicine Center, Baylor College of Medicine, Houston, Texas 77030, USA.
  • Li W; Department of Molecular and Human Genetics, Center for Cell and Gene Therapy, Baylor College of Medicine, Houston, Texas 77030, USA.
  • Goodell MA; Stem Cells and Regenerative Medicine Center, Baylor College of Medicine, Houston, Texas 77030, USA.
Nat Commun ; 8: 16026, 2017 07 11.
Article en En | MEDLINE | ID: mdl-28695892
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.
Asunto(s)

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Proteínas Recombinantes de Fusión / Metilasas de Modificación del ADN / Metilación de ADN / Edición Génica Tipo de estudio: Evaluation_studies Límite: Animals / Humans Idioma: En Revista: Nat Commun Asunto de la revista: BIOLOGIA / CIENCIA Año: 2017 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Proteínas Recombinantes de Fusión / Metilasas de Modificación del ADN / Metilación de ADN / Edición Génica Tipo de estudio: Evaluation_studies Límite: Animals / Humans Idioma: En Revista: Nat Commun Asunto de la revista: BIOLOGIA / CIENCIA Año: 2017 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido