Journal
CELL
Volume 174, Issue 3, Pages 744-+Publisher
CELL PRESS
DOI: 10.1016/j.cell.2018.05.024
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Funding
- HHMI Gilliam Fellowship
- NSF GRFP Fellowship
- NIGMS [T32 GM008042]
- UCLA-Caltech MSTP [NIGMS T32 GM008042]
- NIH 4DN Program [U01 DA040612, U01 HL130007]
- NHGRI GGR Program [U01 HG007910]
- New York Stem Cell Foundation [NYSCF-R-I13]
- Sontag Foundation
- Caltech
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Eukaryotic genomes are packaged into a 3-dimensional structure in the nucleus. Current methods for studying genome-wide structure are based on proximity ligation. However, this approach can fail to detect known structures, such as interactions with nuclear bodies, because these DNA regions can be too far apart to directly ligate. Accordingly, our overall understanding of genome organization remains incomplete. Here, we develop split-pool recognition of interactions by tag extension (SPRITE), a method that enables genome-wide detection of higher-order interactions within the nucleus. Using SPRITE, we recapitulate known structures identified by proximity ligation and identify additional interactions occurring across larger distances, including two hubs of inter-chromosomal interactions that are arranged around the nucleolus and nuclear speckles. We show that a substantial fraction of the genome exhibits preferential organization relative to these nuclear bodies. Our results generate a global model whereby nuclear bodies act as inter-chromosomal hubs that shape the overall packaging of DNA in the nucleus.
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