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Background: Epigenetic processes are proposed to be a mechanism regulating gene expression during phenotypic plasticity. However, environmentally induced changes in DNA methylation exhibit little-to-no association with differential gene expression in metazoans at a transcriptome-wide level. It remains unexplored whether associations between environmentally induced differential methylation and expression are contingent upon other epigenomic processes such as chromatin accessibility. We quantified methylation and gene expression in larvae of the purple sea urchin Strongylocentrotus purpuratus exposed to different ecologically relevant conditions during gametogenesis (maternal conditioning) and modeled changes in gene expression and splicing resulting from maternal conditioning as functions of differential methylation, incorporating covariates for genomic features and chromatin accessibility. We detected significant interactions between differential methylation, chromatin accessibility, and genic feature type associated with differential expression and splicing., Results: Differential gene body methylation had significantly stronger effects on expression among genes with poorly accessible transcriptional start sites while baseline transcript abundance influenced the direction of this effect. Transcriptional responses to maternal conditioning were 4-13 × more likely when accounting for interactions between methylation and chromatin accessibility, demonstrating that the relationship between differential methylation and gene regulation is partially explained by chromatin state., Conclusions: DNA methylation likely possesses multiple associations with gene regulation during transgenerational plasticity in S. purpuratus and potentially other metazoans, but its effects are dependent on chromatin accessibility and underlying genic features., (© 2023. The Author(s).)

Background: Antarctic fishes of the Notothenioidei suborder constitutively upregulate multiple inducible chaperones, a highly derived adaptation that preserves proteostasis in extreme cold, and represent a system for studying the evolution of gene frontloading. We screened for Hsf1-binding sites, as Hsf1 is a master transcription factor of the heat shock response, and highly-conserved non-coding elements within proximal promoters of chaperone genes across 10 Antarctic notothens, 2 subpolar notothens, and 17 perciform fishes. We employed phylogenetic models of molecular evolution to determine whether (i) changes in motifs associated with Hsf1-binding and/or (ii) relaxed purifying selection or exaptation at ancestral cis-regulatory elements coincided with the evolution of chaperone frontloading in Antarctic notothens., Results: Antarctic notothens exhibited significantly fewer Hsf1-binding sites per bp at chaperone promoters than subpolar notothens and Serranoidei, the most closely-related suborder to Notothenioidei included in this study. 90% of chaperone promoters exhibited accelerated substitution rates among Antarctic notothens relative to other perciformes. The proportion of bases undergoing accelerated evolution (i) was significantly greater in Antarctic notothens than in subpolar notothens and Perciformes in 70% of chaperone genes and (ii) increased among bases that were more conserved among perciformes. Lastly, we detected evidence of relaxed purifying selection and exaptation acting on ancestrally conserved cis-regulatory elements in the Antarctic notothen lineage and its major branches., Conclusion: A large degree of turnover has occurred in Notothenioidei at chaperone promoter regions that are conserved among perciform fishes following adaptation to the cooling of the Southern Ocean. Additionally, derived reductions in Hsf1-binding site frequency suggest cis-regulatory modifications to the classical heat shock response. Of note, turnover events within chaperone promoters were less frequent in the ancestral node of Antarctic notothens relative to younger Antarctic lineages. This suggests that cis-regulatory divergence at chaperone promoters may be greater between Antarctic notothen lineages than between subpolar and Antarctic clades. These findings demonstrate that strong selective forces have acted upon cis-regulatory elements of chaperone genes among Antarctic notothens.