Mechanistic insights into allele-specific properties of inter-chromosomal contacts. Mus musculus

The eukaryotic nucleus not only encloses meters of DNA, but also requires DNA to be differentially packaged in a cell-specific manner. Advances in chromosome-capture techniques have made great progress in understanding intra-chromosomal interactions. Yet, the mechanistic identities of homologous or non-homologous inter-chromosomal contacts (HCCs or NHCCs) remain elusive. Recently, two long non-coding RNA loci, CISTR-ACT and FIRRE, have been observed at NHCCs and implicated in human disease. Based on single nucleotide polymorphisms (SNPs), we developed an allele-specific CRISPR live-cell DNA imaging technique, named SNP-CLING, to describe primary locus characteristics across space and time. We observed allele-specific gene positioning, frequencies of HCCs or NHCCs, their motility and stability, and their positioning at the distinct sub-nuclear compartment of the nucleolus. Collectively, we define allele-specific locus properties and dynamics, and uncover an important new layer of genome organization in live cells. Overall design: Allele-specific Hi-C in 129xCast mouse embryonic fibroblasts