Cell https://doi.org/10.1016/j.cell.2018.05.024 (2018)
The intra- and interchromatin interactions in a cell provide a delicate layer of gene expression regulation. To detect multiple genome-wide and long-range DNA interactions occurring simultaneously within the nucleus, Quinodoz et al. developed the split-pool recognition of interactions by tag extension (SPRITE) method. SPRITE enables the interacting molecules within an individual complex to be uniquely barcoded and determined by sequencing and matching all reads with identical barcodes. Using this method, they quantitatively measured long genomic distance interactions and identified two major interchromosomal hubs arranged around nuclear bodies. By extending SPRITE to simultaneously measure DNA and RNA interactions, they identified an active hub with high gene density and active transcription around nuclear speckles, while the inactive hub was detected near the centromere in the vicinity of the nucleolus. The regional density of Pol II transcription rather than transcriptional activity of individual genes determined the proximity to nuclear bodies. Overall, this study provides a useful tool for characterizing the spatial organization of the global genome and further understanding of chromatin structure and gene expression regulation.