Genome-wide chromatin interaction profiling reveals vital role of super-enhancers and rearrangements in host enhancer contacts during BmNPV infection

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, due to the lack of 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 generated the genome-wide enhancer-gene map of silkworm, and identified super-enhancers with the role in regulating the expression of vital genes related to cell state maintenance through the sophisticated interaction network. Additionally, a radical attenuation in chromatin interaction was found after infection of Bombyx mori nucleopolyhedrovirus (BmNPV), the main pathogen of silkworm, which directly rearranged the enhancer contacts. Such rearrangement disturbed the intrinsic enhancer-gene connections in several antiviral genes, resulting in reduced expression of these genes, which thereby accelerated viral infection. Overall, our results reveal the significant regulatory role of super-enhancers and shed new lights on the mechanisms and dynamic changes of the genome-wide enhancer regulatory network.