Multilayered epigenetic regulation of iron homeostasis in plants: From chromatin remodeling to genome engineering

Iron (Fe) deficiency is a major nutritional disorder that restricts plant growth, reduces crop productivity, and contributes to insufficient dietary Fe intake in humans. Alongside well-characterized transcriptional and physiological mechanisms, plants employ epigenetic processes as regulatory layers that modulate Fe homeostasis. DNA methylation, histone modifications, and RNA-mediated pathways reshape chromatin and fine-tune Fe-responsive gene expression, enabling rapid adaptation to fluctuating Fe supply. Evidence across plant systems indicates that dynamic DNA methylation modulates Fe uptake and redistribution pathways, whereas histone methylation, acetylation, and variant incorporation remodel chromatin to activate or repress Fe transporters and their transcriptional regulators. Small RNAs and long non-coding RNAs are potential regulators of local and systemic Fe signaling, but their precise targets and mechanisms remain unclear. These epigenetic processes establish stress memory that primes plants for heightened responsiveness to subsequent Fe limitation. This review synthesizes advances in plant epigenetics to highlight how multilayered chromatin remodeling and RNA-based regulation orchestrate Fe deficiency responses and homeostasis. The review evaluates translational applications of genome and epigenome engineering, including CRISPR-based editing and targeted epigenetic modulation, as strategies for crop Fe biofortification. Linking mechanistic insights with applied strategies positions epigenetic regulation as a central avenue for improving plant resilience to Fe deficiency and advancing sustainable agriculture and global nutritional security.