Inter-chromosomal Contact Properties in Live-Cell Imaging and in Hi-C.
Imaging (fluorescence in situ hybridization [FISH]) and genome-wide chromosome conformation capture (Hi-C) are two major approaches to the study of higher-order genome organization in the nucleus. Intra-chromosomal and inter-chromosomal interactions (referred to as non-homologous chromosomal contacts [NHCCs]) have been observed by several FISH-based studies, but locus-specific NHCCs have not been detected by Hi-C. Due to crosslinking, neither of these approaches assesses spatiotemporal properties. Toward resolving the discrepancies between imaging and Hi-C, we sought to understand the spatiotemporal properties of NHCCs in living cells by CRISPR/Cas9 live-cell imaging (CLING). In mammalian cells, we find that NHCCs are stable and occur as frequently as intra-chromosomal interactions, but NHCCs occur at farther spatial distance that could explain their lack of detection in Hi-C. By revealing the spatiotemporal properties in living cells, our study provides fundamental insights into the biology of NHCCs.
|Year of Publication||
2018 03 15
|PubMed Central ID||
P01 GM099117 / GM / NIGMS NIH HHS / United States
R01 MH102416 / MH / NIMH NIH HHS / United States
U01 DA040612 / DA / NIDA NIH HHS / United States
HHMI / Howard Hughes Medical Institute / United States