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

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

*Corresponding author for this work

Research output: Chapter in Book/Report/Conference proceedingChapterAcademicpeer-review

5 Citations (Scopus)
101 Downloads (Pure)

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.

Original languageEnglish
Title of host publicationDNA Methyltransferases - Role and Function
EditorsAlbert Jeltsch, Renata Z. Jurkowska
PublisherSpringer
Chapter18
Pages515-533
Number of pages19
ISBN (Electronic)978-3-031-11454-0
ISBN (Print)978-3-031-11453-3
DOIs
Publication statusPublished - 2022

Publication series

NameAdvances in experimental medicine and biology
Volume1389
ISSN (Print)0065-2598

Keywords

  • CpG methylation
  • CRISPR-dCas9
  • DNMT
  • Epigenetic editing
  • TALE
  • Zinc finger

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