RT Journal
A1 Huang, Ni
A1 Seow, Wei Qiang
A1 Appert, Alex
A1 Dong, Yan
A1 Stempor, Przemyslaw
A1 Ahringer, Julie
T1 Accessible Region Conformation Capture (ARC-C) gives high-resolution insights into genome architecture and regulation
JF Genome Research 
JO Genome Research 
YR 2022 
FD February 01 
VO 32 
IS 2 
SP 357 
OP 366 
DO 10.1101/gr.275669.121 
UL http://genome.cshlp.org/content/32/2/357.abstract 
AB Nuclear organization and chromatin interactions are important for genome function, yet determining chromatin connections at high resolution remains a major challenge. To address this, we developed Accessible Region Conformation Capture (ARC-C), which profiles interactions between regulatory elements genome-wide without a capture step. Applied to Caenorhabditis elegans, ARC-C identifies approximately 15,000 significant interactions between regulatory elements at 500-bp resolution. Of 105 TFs or chromatin regulators tested, we find that the binding sites of 60 are enriched for interacting with each other, making them candidates for mediating interactions. These include cohesin and condensin II. Applying ARC-C to a mutant of transcription factor BLMP-1 detected changes in interactions between its targets. ARC-C simultaneously profiles domain-level architecture, and we observe that C. elegans chromatin domains defined by either active or repressive modifications form topologically associating domains (TADs) that interact with A/B (active/inactive) compartment-like structure. Furthermore, we discover that inactive compartment interactions are dependent on H3K9 methylation. ARC-C is a powerful new tool to interrogate genome architecture and regulatory interactions at high resolution.