Rewriting DNA Methylation Signatures at Will: The Curable Genome Within Reach?
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.
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
S
Stolzenburg
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.
Désirée
D
Goubert
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. m.g.rots@umcg.nl.
Marianne G
MG
Rots
D004247:DNA / Q000235:genetics*; D019175:DNA Methylation / Q000235:genetics*; D044127:Epigenesis, Genetic; D000072669:Gene Editing; D005786:Gene Expression Regulation / Q000235:genetics*; D020868:Gene Silencing; D015894:Genome, Human; D006801:Humans; D058990:Molecular Targeted Therapy; D012313:RNA
D012313:RNA; D004247:DNA