Histone modifications are essential regulators of chromatin architecture and gene expression in plants. Traditionally, each modification was viewed as an independent signal marking specific chromatin states. However, recent advances in epigenome profiling, genome editing, and proteomics have revealed that histone marks often function in combination, engaging in hierarchical, cooperative, and antagonistic relationships. In particular, studies in Arabidopsis thaliana have uncovered dynamic interactions between activating and repressive modifications, as well as their coordination with DNA methylation, histone variants, and RNA modifications. Among these, H3K4 and H3K36 methylation have emerged as key regulatory hubs that integrate developmental and environmental signals into context-dependent transcriptional responses. This growing body of evidence suggests that chromatin regulation involves not isolated modifications but rather a complex network of interdependent marks. In this review, we discuss recent examples of crosstalk between histone modifications and other regulatory layers to highlight how combinatorial chromatin regulation and its underlying molecular mechanisms contribute to transcriptional control and epigenetic responsiveness in plants. Such key insights expand our understanding of the diverse and context-dependent roles of histone modifications in plant biology.
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