| Summary: | Abstract Background Bungarus multicinctus, from which a classical Chinese medicine is produced, is known as the most venomous land snake in the world, but the chromatin organization and transcription factor activity during venom replenishment progress have not been explored yet. This study aimed to determine the roles of chromatin structure in toxin activity via bioinformatics and experimental validation. Methods Chromosome conformation capture (Hi-C) analysis was used to examine interactions among chromosomes and identify different scales of chromatin during envenomation in B. multicinctus. Correlations between epigenetic modifications and chromatin structure were verified through ChIP-seq analysis. RNA-seq was used to validate the influence of variation in chromatin structure and gene expression levels on venom production and regulation. Results Our results suggested that intra-chromosomal interactions are more intense than inter-chromosomal interactions among the control group, 3-day group of venom glands and muscles. Through this, we found that compartmental transition was correlated with chromatin interactions. Interestingly, the up-regulated genes in more compartmental switch regions reflect the function of toxin activity. Topologically associated domain (TAD) boundaries enriched with histone modifications are associated with different distributions of genes and the expression levels. Toxin-coding genes in the same loop are highly expressed, implying that the importance of epigenetic regulation during envenomination. On a smaller scale, the epigenetic markers affect transcriptional regulation by controlling the recruitment/inhibition of transcription initiation complexes. Conclusions Chromatin structure and epigenetic modifications could play a vital status role in the mechanisms of venom regulation in B. multicinctus.
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