HiChIRP reveals RNA-associated chromosome conformation

Modular domains of lncRNAs can serve as scaffolds to bring distant regions of the linear genome into spatial proximity. Here we present HiChIRP, a method leveraging novel bioorthogonal chemistry and customized 3C conditions, that enables interrogation of chromatin architecture focused around a specific RNA of interest down to ~10 copies per cell. HiChIRP of three nuclear RNAs reveal insights into promoter interactions (7SK), telomere biology (TERC), and inflammatory gene regulation (lincRNA-EPS). Overall design: HiChIP of CTCF in GM12878 cells. HiChIP of Oct4 in mESCs. HiChIRP of 7SK in mESCs. HiChIRP of TERC in GM12878 cells. HiChIRP of lincRNA-EPS, HiChIP of H3K4me3 and SMC1a, and Hi-C in BMDM wild-type cells. HiChIP of H3K4me3 and SMC1a in lincRNA-EPS KO BMDM cells. ChIRP-seq of lincRNA-EPS in BMDM wild-type cells.