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Rewriting DNA Methylation Signatures at Will: The Curable Genome Within Reach?

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DNA Methyltransferases - Role and Function

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 945))

Abstract

Epigenetic regulation of gene expression is vital for the maintenance of genome integrity and cell phenotype. In addition, many different diseases have underlying epigenetic mutations, and understanding their role and function may unravel new insights for diagnosis, treatment, and even prevention of diseases. It was an important breakthrough when epigenetic alterations could be gene-specifically manipulated using epigenetic regulatory proteins in an approach termed epigenetic editing. Epigenetic editors can be designed for virtually any gene by targeting effector domains to a preferred sequence, where they write or erase the desired epigenetic modification. This chapter describes the tools for editing DNA methylation signatures and their applications. In addition, we explain how to achieve targeted DNA (de)methylation and discuss the advantages and disadvantages of this approach. Silencing genes directly at the DNA methylation level instead of targeting the protein and/or RNA is a major improvement, as repression is achieved at the source of expression, potentially eliminating the need for continuous administration. Re-expression of silenced genes by targeted demethylation might closely represent the natural situation, in which all transcript variants might be expressed in a sustainable manner. Altogether epigenetic editing, for example, by rewriting DNA methylation, will assist in realizing the curable genome concept.

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Abbreviations

ATF:

Artificial transcription factor

ChIP:

Chromatin immunoprecipitation

CpG:

Cytosine–phosphate–guanine

CRISPRs:

Clustered regulatory interspaced palindromic repeats

DNMT:

DNA methyltransferase

ncRNA:

Nonprotein-coding RNA

sgRNA:

Single-guide RNA

TALEs:

Transcription activator-like effectors

TDG:

Thymidine–DNA glycosylase

TET:

Ten–eleven translocation

ZF:

Zinc finger

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Acknowledgments

We would like to acknowledge the EU funding for D.G. (H2020-MSCA-ITN-2014-ETN 642691 EpiPredict). M.G.R. serves as vice-chair of H2020-COST CM1406, and her team is partially funded by NWO-Vidi-91786373 and EU-FP7-SNN-4D22C-T2007.

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Authors and Affiliations

  1. Epigenetic Editing Research Group, Department of Pathology and Medical Biology, University Medical Center Groningen, University of Groningen, Hanzeplein 1 EA11, Groningen, 9713 GZ, The Netherlands

    Sabine Stolzenburg, Désirée Goubert & Marianne G. Rots

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  1. Sabine Stolzenburg
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  2. Désirée Goubert
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  3. Marianne G. Rots
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Correspondence to Marianne G. Rots .

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Editors and Affiliations

  1. Institut für Biochemie, Universität Stuttgart, Stuttgart, Germany

    Albert Jeltsch

  2. BioMed X Innovation Center, Heidelberg, Germany

    Renata Z. Jurkowska

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Stolzenburg, S., Goubert, D., Rots, M.G. (2016). Rewriting DNA Methylation Signatures at Will: The Curable Genome Within Reach?. In: Jeltsch, A., Jurkowska, R. (eds) DNA Methyltransferases - Role and Function. Advances in Experimental Medicine and Biology, vol 945. Springer, Cham. https://doi.org/10.1007/978-3-319-43624-1_17

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