Epigenome editing: a dimension of genome editing beyond DNA sequence

Abstract

Epigenome editing has emerged as a transformative extension of conventional genome engineering, offering precise and programmable control of gene expression without altering the underlying DNA sequence. In contrast to the genetic modifications that introduce permanent sequence changes, epigenome editing exploits reversible and potentially heritable epigenetic mechanisms such as DNA methylation, histone modifications, chromatin remodelling, and RNA-mediated gene silencing to regulate transcriptional states. Advances in next-generation sequencing technologies have enabled high-resolution mapping of epigenetic landscapes, revealing the dynamic and context-dependent nature of chromatin regulation across development and environmental conditions. The integration of programmable DNA-binding platforms, including zinc finger proteins, transcription activator-like effectors, and CRISPR/dCas9-based systems, with epigenetic effector domains has revolutionized locus specific manipulation of chromatin states. These tools facilitate targeted gene activation or repression (CRISPRa/CRISPRi), as well as direct rewriting of epigenetic marks, providing unprecedented opportunities to dissect gene regulatory networks and trait expression. In plants, epigenome editing has shown particular promise for functional genomics, stress adaptation, and crop improvement, enabling fine-tuning of agriculturally important traits such as yield, quality, and stress tolerance. This review comprehensively discusses the molecular mechanisms underlying epigenetic regulation, key epigenome editing tools, their modes of action, and the emerging applications of epigenome editing in plant biology, highlighting it as a potential tool for sustainable agriculture and precision breeding. This review provides a comprehensive and integrated perspective on epigenome editing by linking molecular mechanisms, advanced editing tools, and practical applications in plant systems, thereby offering a foundation for future research and the development of climate-resilient and sustainable crop improvement strategies.