High-resolution mapping of regulatory element interactions and genome architecture using ARC-C [ARC-C]

Interactions between cis-regulatory elements such as promoters and enhancers are important for transcription but global identification of these interactions remains a major challenge. Leveraging the chromatin accessiblity of regulatory elements, we developed ARC-C (accessible region chromosome conformation capture), which profiles chromatin regulatory interactions genome-wide at high resolution. Applying ARC-C to C. elegans, we identify ~15,000 significant interactions at 500bp resolution. Regions bound by transcription factors and chromatin regulators such as cohesin and condensin II are enriched for interactions, and we use ARC-C to show that the BLMP-1 transcription factor mediates interactions between its targets. Investigating domain level architecture, we find that C. elegans chromatin domains defined by either active or repressive modifications form topologically associating domains (TADs) and that these domains interact to form A/B (active/inactive) compartment structure. ARC-C is a powerful new tool to interrogate genome architecture and regulatory interactions at high resolution. Overall design: We performed ARC-C in wildtype, blmp-1 and met2set25 C elegans L3 larvae.