期刊
CELL
卷 173, 期 5, 页码 1165-+出版社
CELL PRESS
DOI: 10.1016/j.cell.2018.03.072
关键词
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资金
- NIAMS
- NCI
- NIAID funding
- NIH Helix Systems
- Paul and Daisy Soros Fellowship
- Fannie and John Hertz Foundation Fellowship
- Cornelia de Lange Syndrome Foundation
- NIH New Innovator Award [1DP2OD008540-01]
- NSF Physics Frontiers Center Award [PHY-1427654]
- NHGRI Center for Excellence for Genomic Sciences [HG006193]
- Welch Foundation [Q-1866, C-1792]
- NVIDIA Research Center Award
- IBM University Challenge Award
- Google Research Award
- Cancer Prevention Research Institute of Texas Scholar Award [R1304]
- USDA Agriculture and Food Research Initiative Grant [2017-05741]
- McNair Medical Institute Scholar Award
- NIH Encyclopedia of DNA Elements Mapping Center Award [UM1HG009375]
- President's Early Career Award in Science and Engineering
- NSF [PHY-1427654, CHE-1614101]
- Div Of Molecular and Cellular Bioscience
- Direct For Biological Sciences [1614101] Funding Source: National Science Foundation
Cohesin extrusion is thought to play a central role in establishing the architecture of mammalian genomes. However, extrusion has not been visualized in vivo, and thus, its functional impact and energetics are unknown. Using ultra-deep Hi-C, we show that loop domains form by a process that requires cohesin ATPases. Once formed, however, loops and compartments are maintained for hours without energy input. Strikingly, without ATP, we observe the emergence of hundreds of CTCF-independent loops that link regulatory DNA. We also identify architectural stripes,'' where a loop anchor interacts with entire domains at high frequency. Stripes often tether super-enhancers to cognate promoters, and in B cells, they facilitate Igh transcription and recombination. Stripe anchors represent major hotspots for topoisomerase-mediated lesions, which promote chromosomal translocations and cancer. In plasmacytomas, stripes can deregulate Igh-translocated oncogenes. We propose that higher organisms have coopted cohesin extrusion to enhance transcription and recombination, with implications for tumor development.
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