Shudi Zhao1,2, Yuedong Li1,2, Guanping Chen1,2, Xingyang Wang1,2, Nan Chen1,2 and Xiaofeng Wu1,2 1College of Animal Sciences, Zhejiang University, Hangzhou 310058, China; 2Key Laboratory of Silkworm and Bee Resource Utilization and Innovation of Zhejiang Province, Hangzhou 310058, China Corresponding author: wuxiaofengzju.edu.cn Abstract

As influential regulatory elements in the genome, enhancers control gene expression under specific cellular conditions, and such connections are dynamic under different conditions. However, because of the lack of a genome-wide enhancer–gene connection map, the roles and regulatory pattern of enhancers were poorly investigated in insects, and the dynamic changes of enhancer contacts and functions under different conditions remain elusive. Here, combining Hi-C, ATAC-seq, and H3K27ac ChIP-seq data, we generate the genome-wide enhancer–gene map of silkworm and identify super-enhancers with a role in regulating the expression of vital genes related to cell state maintenance through a sophisticated interaction network. Additionally, a radical attenuation of chromatin interactions is found after infection of Bombyx mori nucleopolyhedrovirus (BmNPV), the main pathogen of silkworm, which directly rearranges the enhancer contacts. Such a rearrangement disturbs the intrinsic enhancer–gene connections in several antiviral genes, resulting in reduced expression of these genes, which accelerates viral infection. Overall, our results reveal the regulatory role of super-enhancers and shed new light on the mechanisms and dynamic changes of the genome-wide enhancer regulatory network.

Received March 28, 2023. Accepted October 14, 2023.