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Gene-Targeted DNA Methylation: Towards Long-Lasting Reprogramming of Gene Expression?

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DNA Methyltransferases - Role and Function

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 1389))

Abstract

DNA methylation is an essential epigenetic mark, strongly associated with gene expression regulation. Aberrant DNA methylation patterns underlie various diseases and efforts to intervene with DNA methylation signatures are of great clinical interest. Technological developments to target writers or erasers of DNA methylation to specific genomic loci by epigenetic editing resulted in successful gene expression modulation, also in in vivo models. Application of epigenetic editing in human health could have a huge impact, but clinical translation is still challenging. Despite successes for a wide variety of genes, not all genes mitotically maintain their (de)methylation signatures after editing, and reprogramming requires further understanding of chromatin context-dependency. In addition, difficulties of current delivery systems and off-target effects are hurdles to be tackled. The present review describes findings towards effective and sustained DNA (de)methylation by epigenetic editing and discusses the need for multi-effector approaches to achieve highly efficient long-lasting reprogramming.

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Acknowledgements

The authors thank Sabine Stolzenburg for her assistance in writing the chapter on targeted methylation in the earlier book version (Stolzenburg et al. 2016). FCM acknowledges his Scholarship funding from the Colombian Ministry of Science, Technology and Innovation (Minciencias -COLCIENCIAS/COLFUTURO-Doctorados en el exterior 2017 N°783) and Instituto Tecnológico Metropolitano (ITM). FS is supported by VALERE program, Vanvitelli per la Ricerca. H2020 European Cooperation in Science and Technology (COST) Training Actions (www.INC-COST.eu and www.EpiChemBio.eu) are acknowledged for facilitating network activities.

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Author notes

  1. Fabian M. Cortés-Mancera and Federica Sarno contributed equally.

Authors and Affiliations

  1. Epigenetic Editing, Department of Pathology and Medical Biology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands

    Fabian M. Cortés-Mancera, Federica Sarno, Désirée Goubert & Marianne G. Rots

  2. Grupo de Investigación e Innovación Biomédica, Departamento de Ciencias Aplicadas, Instituto Tecnológico Metropolitano, Medellín, Colombia

    Fabian M. Cortés-Mancera

  3. Dipartimento di Medicina di Precisione, Universita degli Studi della Campania “Luigi Vanvitelli” Napoli, Napoli, Italy

    Federica Sarno

Authors
  1. Fabian M. Cortés-Mancera
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  2. Federica Sarno
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  3. Désirée Goubert
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  4. Marianne G. Rots
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Corresponding author

Correspondence to Marianne G. Rots .

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Editors and Affiliations

  1. Department of Biochemistry, Institute of Biochemistry and Technical Biochemistry, University of Stuttgart, Stuttgart, Germany

    Albert Jeltsch

  2. School of Biosciences, Division of Biomedicine, Cardiff University, Cardiff, UK

    Renata Z. Jurkowska

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Cortés-Mancera, F.M., Sarno, F., Goubert, D., Rots, M.G. (2022). Gene-Targeted DNA Methylation: Towards Long-Lasting Reprogramming of Gene Expression?. In: Jeltsch, A., Jurkowska, R.Z. (eds) DNA Methyltransferases - Role and Function. Advances in Experimental Medicine and Biology, vol 1389. Springer, Cham. https://doi.org/10.1007/978-3-031-11454-0_18

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