Jul 2026· Saudi Journal of Food Security and Environmental Sustainability· Vol 1· 0 citations· 75 references
TL;DR
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.
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.
Although cells within an organism share nearly identical genomes, their transcriptional programs differ markedly due to reversible chemical modifications known as epigenetic marks. These marks, including DNA methylation and histone modifications, regulate gene expression without altering DNA sequence and play a central role in development and disease. While epigenetic drugs such as DNA methyltransferase inhibitors have shown clinical benefit, their genome-wide activity often results in off-target toxicity limiting broader therapeutic applications. This has driven the development of locus-specific epigenetic editing strategies. Programmable epigenetic modifiers (PEMs) combine customizable DNA-binding platforms, such as CRISPR-dCas systems, transcription activator-like effectors (TALEs), or zinc fingers, with epigenetic effector domains to precisely install or remove regulatory marks at defined genomic loci. Because effective editing depends on the pre-existing epigenetic landscape, detection and characterization of target-site epigenetic states is a prerequisite for rational editor design, increasingly aided by machine-learning models that predict editing outcomes. In this review, we summarize current technologies for epigenetic mark detection and discuss the transition from global pharmacological approaches to programmable, modular editing systems that enable spatial and temporal control of gene regulation. We further address heritability and delivery constraints. Reversible, site-specific epigenetic editing represents a promising therapeutic paradigm for cancer, genetic disorders, and regenerative medicine.
Genomic manipulation has advanced from stochastic nuclease‐mediated disruption toward programmable, deterministic precision. Early clustered regularly interspaced short palindromic repeats (CRISPR) strategies enabled targeted mutagenesis through double‐strand breaks; however, their therapeutic application is limited by genotoxicity, chromosomal instability, and dependence on endogenous repair pathways that are difficult to predict. In this review, we examined the transition from gene editing to genome writing, an approach that decouples genomic modification from host repair pathways to better balance efficiency, precision, and payload delivery. We also discussed the principles of precision technologies, including base and prime editors, and described emerging large‐scale writers, such as CRISPR‐associated transposases and recombinase‐based bridge RNAs, which enable the integration of multi‐kilobase synthetic modules. Beyond enzymatic mechanisms, we further considered the combined use of generative artificial intelligence, structural biology, and novel delivery architectures as potential strategies to overcome current biological limitations. Taken together, these developments point toward Generative Biology, in which computational design and high‐throughput screening transform the genome from a static substrate into a more dynamic model for complex, synthetic functional design.
Cell-specific epigenetic editing holds very high therapeutic value for atherosclerosis, cardiomyopathy, and fibrosis, provided that delivery, specificity, and safety challenges are also addressed.
Majed Alsulami, Mahmood Rasool, Ahmed Masoud et al.· The Cardiology· 0 citations
SunTag-NOVA robustly installed DNA methylation and repressed transcription at the endogenous FWA, FT and TMM genes with minimal genome-wide off-target consequences, and establishes SunTag-NOVA as a specific epigenome-editing platform for plants.
Yan He, Ming Wang, T. J. Buckley et al.· bioRxiv· 0 citations
This chapter outlines a comprehensive methodology for the design, assembly, and functional assessment of CRISPR/dCas9 systems optimized for tomato to investigate pathogen-associated responses.
Ananya Mukherjee, Shrabani Basak, Raghuvir Singh et al.· Methods in molecular biology· 0 citations
Cells in multicellular eukaryotic systems are diverse biological units, with characteristics and functions determined by their molecular profiles. CRISPR–Cas9 genome editing has been widely used across biology to modulate gene expression and study gene function. However, there is currently no versatile and scalable method for editing a cell’s genome in response to endogenous cellular signals. Here, we report the engineering of a CRISPR guide RNA that efficiently confers genome editing in response to the catalytic activity of a target microRNA (miRNA) within a cell. miRNAs are short non-coding RNAs that are widely conserved across eukaryotes and can cleave their target RNA through almost perfect base pairing. In mammals, miRNAs are largely involved in development and homeostasis as well as disease progression and developmental disorders. To leverage these properties for genome editing, we developed a cuffed guide RNA (cgRNA) which is composed of a permutated order of sequence domains from the commonly used single guide RNA (sgRNA). These permutated domains were then concatenated with a miRNA target sequence, yielding a warped guide RNA that is inactive until cleaved by a complementary miRNA. We demonstrated that cgRNA enabled efficient miRNA activity-dependent genome editing in human and mouse cell lines. Biochemical and structural analyses revealed three stages of inhibition of the CRISPR genome-editing pathway for unprocessed cgRNA. Utilizing a lentiviral library of cgRNAs containing miRNA targets covering mouse genome-wide miRNAs, we identified miRNA cleavage activities and their sequence specificities in mouse embryonic stem cells and during smooth muscle cell differentiation. Furthermore, we showed that endogenous mRNA expression could be irreversibly recorded into a DNA sequence using a cgRNA targeted by a synthetic miRNA repeat. cgRNA is a simple, robust, miRNA activity-gated genome editing system that could facilitate the development of cell state-specific genome editing, the mapping of miRNA activity and gene expression landscapes, and the recording of molecularly determined cell states during the long-term progression of multicellular systems.
Arman Adel, Yuta Shuto, Shunsuke Kawasaki et al.· bioRxiv· 0 citations