Epigenetic Modulators in Plants: Mechanistic Insights, Screening Approaches, and Prospective Applications

Epigenetic regulation governs plant growth, development, and environmental adaptation through dynamic control and stress memory mechanisms. However, research and application of plant epigenetics face several limitations. Functional redundancy within epigenetic gene families obscures phenotypic changes resulting from single-gene mutagenesis. Loss-of-function mutations in core epigenetic factors frequently lead to seedling or gametophytic lethality, thereby restricting forward genetic screening. Additionally, technical limitations in genetic transformation impede the translation of findings from model plants to a diverse range of agricultural and horticultural crops. In animal systems, epigenetic small-molecule modulators have been developed to manipulate cell totipotency and advance regenerative research, underscoring the potential of chemical genetics strategies. In contrast, the development of plant epigenetic modulators still lag behind. Given the evolutionary conservation of epigenetic pathways across animals and plants, this review summarizes characterized animal epigenetic modulators for potential use in plant epigenetic studies. Furthermore, acknowledging the divergence in epigenetic regulatory components and cascades between plants and animals, we outline strategies to generate plant epigenetic modulators by leveraging technical frameworks established for plant growth regulator development. This work aims to expand the chemical toolbox for plant epigenetics and accelerate both fundamental research and agricultural applications of epigenetic knowledge.