Understanding how medicinal plants adapt to global warming, particularly through epigenetic mechanisms that modify phenotypes without changing DNA sequences is crucial. Scrophularia ningpoensis Hemsl., a traditional Chinese Medicine (TCM), produces bioactive compounds that are influenced by environmental temperatures, making it an ideal model for studying the biological basis of TCM geoherbalism. However, the adaptive potential of epigenetic marks in S. ningpoensis under varying temperatures remains understudied, partly due to the absence of a reference genome. Here, it was demonstrated that mild warm temperatures contribute to the metabolic accumulation and the cultivated migration of S. ningpoensis using a global dataset. A high-quality chromosome-level genome was assembled, and an atlas of epigenetic, metabolic, and transcriptomic profiles across different tissues. Transcriptome analysis identified 3401 allele-specific expressed genes (ASEGs) across nine tissues by comparing two haplotypes. ChIP-seq and BS-seq data from leaf and root tissues revealed that ASEGs are associated with distinct epigenetic patterns, particularly the active mark H3K36me3, which functions differently in these tissues. Notably, genes marked with H3K36me3 in iridoid synthesis pathway predominantly expressed in roots. Additionally, the histone methyltransferase SnSDG8 was identified to regulate ectopic H3K36me3 in iridoid biosynthesis in response to warming temperatures. Our results highlight the epigenetic mechanisms of global warming on herb-derived products, significant for medicinal plant breeding under temperature stress.

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