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Re-expressing Epigenetically Silenced Genes by Inducing DNA Demethylation Through Targeting of Ten-Eleven Translocation 2 to Any Given Genomic Locus

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Functional Genomics

Part of the book series: Methods in Molecular Biology ((MIMB,volume 1654))

Abstract

Epigenetic editing is a novel methodology to modify the epigenetic landscape of any genomic location. As such, the approach might reprogram expression profiles, without altering the DNA sequence. Epigenetic alterations, including promoter hypermethylation, are associated with an increasing number of human diseases. To exploit this situation, epigenetic editing rises as a new alternative to specifically demethylate abnormally hypermethylated regions. Here, we describe a methodology to actively demethylate the hypermethylated ICAM-1 promoter. Reducing DNA methylation in our target region increased the expression of the ICAM-1 gene. As the ICAM-1 gene in our cell lines was highly methylated (up to 80%), this approach proves a robust manner to reduce methylation for hypermethylated regions. Epigenetic editing therefore not only provides an approach to address mechanisms of gene expression regulation, but also adds to the therapeutic toolbox as current inhibitors of epigenetic enzymes are limited by genome-wide effects.

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Author information

Authors and Affiliations

  1. Epigenetic Editing Research Group, Department of Pathology and Medical Biology, University of Groningen, University Medical Centre Groningen, Hanzeplein, 9713 GZ, Groningen, The Netherlands

    Julio Cesar Rendón, David Cano-Rodríguez & Marianne G. Rots

Authors
  1. Julio Cesar Rendón
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  2. David Cano-Rodríguez
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  3. Marianne G. Rots
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Corresponding author

Correspondence to Marianne G. Rots .

Editor information

Editors and Affiliations

  1. Chair of Biochemistry and Molecular Medicine, Division of Functional Genomics, Faculty of Health, School of Medicine, Center for Biochemical Research and Education ZBAF, Witten/Herdecke University, Witten, Germany

    Michael Kaufmann

  2. Chair of Biochemistry and Molecular Medicine, Division of Functional Genomics, Faculty of Health, School of Medicine, Center for Biochemical Research and Education ZBAF, Witten/Herdecke University, Witten, Germany

    Claudia Klinger

  3. Chair of Biochemistry and Molecular Medicine, Division of Functional Genomics, Faculty of Health, School of Medicine, Center for Biochemical Research and Education ZBAF, Witten/Herdecke University, Witten, Germany

    Andreas Savelsbergh

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Rendón, J.C., Cano-Rodríguez, D., Rots, M.G. (2017). Re-expressing Epigenetically Silenced Genes by Inducing DNA Demethylation Through Targeting of Ten-Eleven Translocation 2 to Any Given Genomic Locus. In: Kaufmann, M., Klinger, C., Savelsbergh, A. (eds) Functional Genomics. Methods in Molecular Biology, vol 1654. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-7231-9_24

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  • DOI: https://doi.org/10.1007/978-1-4939-7231-9_24

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  • Publisher Name: Humana Press, New York, NY

  • Print ISBN: 978-1-4939-7230-2

  • Online ISBN: 978-1-4939-7231-9

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