Regulatory elements can be essential for maintaining broad chromatin organization and cell viability

Increasing evidence shows that promoters and enhancers could be related to 3D chromatin structure, thus affecting cellular functions. Except for their roles in forming canonical chromatin loops, promoters and enhancers have not been well studied regarding the maintenance of broad chromatin organization. Here, we focused on the active promoters/enhancers predicted to form many 3D contacts with other active promoters/enhancers (referred to as hotspots) and identified dozens of loci essential for cell growth and survival through CRISPR screening. We found that the deletion of an essential hotspot could lead to changes in broad chromatin organization and the expression of distal genes. We showed that the essentiality of hotspots does not result from their association with individual genes that are essential for cell viability but rather from their association with multiple dysregulated non-essential genes to synergistically impact cell fitness.

Automated summary

Increasing evidence suggests that promoters and enhancers are closely associated with the 3D chromatin structure and have an impact on cellular functions. This study investigated the role of active promoters/enhancers that are predicted to form multiple 3D contacts with other active promoters/enhancers. The findings showed that these hotspots are essential for cell growth and survival, and their deletions result in changes in broad chromatin organization and the expression of distal genes. The essentiality of these hotspots is attributed to their association with multiple dysregulated non-essential genes that collectively affect cell fitness.