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

  • Sabine Stolzenburg
  • Désirée Goubert
  • Marianne G. RotsEmail author
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 945)


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.


Zinc Finger Zinc Finger Protein SOX2 Promoter Heterochromatic Gene CDKN2A Locus 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



Artificial transcription factor


Chromatin immunoprecipitation




Clustered regulatory interspaced palindromic repeats


DNA methyltransferase


Nonprotein-coding RNA


Single-guide RNA


Transcription activator-like effectors


Thymidine–DNA glycosylase


Ten–eleven translocation


Zinc finger



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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Copyright information

© Springer International Publishing Switzerland 2016

Authors and Affiliations

  • Sabine Stolzenburg
    • 1
  • Désirée Goubert
    • 1
  • Marianne G. Rots
    • 1
    Email author
  1. 1.Epigenetic Editing Research Group, Department of Pathology and Medical BiologyUniversity Medical Center Groningen, University of GroningenGroningenThe Netherlands

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