期刊
MOLECULAR CELL
卷 67, 期 6, 页码 1037-+出版社
CELL PRESS
DOI: 10.1016/j.molcel.2017.08.006
关键词
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资金
- NIH National Human Genome Research Institute (NHGRI) [R00HG008662]
- Damon Runyon Cancer Research Foundation [DRG-2122-12]
- NIH National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) [F32DK107112]
- NIH [T32HG000044]
- NIH National Cancer Institute (NCI) [CA142538-07]
- NIH T32 fellowship [HG000044]
- Genentech Graduate Fellowship
- NIH Centers of Excellence in Genomic Science (CEGS) [5P50HG00773502]
- NIH New Innovator Award [1DP2OD008540]
- NSF Physics Frontiers Center Award [PHY-1427654]
- NHGRI Center for Excellence for Genomic Sciences [HG006193]
- Welch Foundation [Q-1866]
- NVIDIA Research Center Award
- IBM University Challenge Award
- Google Research Award
- Cancer Prevention Research Institute of Texas Scholar Award [R1304]
- McNair Medical Institute Scholar Award
- NIH (4D Nucleome grant) [U01HL130010]
- NIH (NIH Encyclopedia of DNA Elements Mapping Center Award) [UM1HG009375]
- President's Early Career Award in Science and Engineering
The three-dimensional arrangement of the human genome comprises a complex network of structural and regulatory chromatin loops important for coordinating changes in transcription during human development. To better understand the mechanisms underlying context-specific 3D chromatin structure and transcription during cellular differentiation, we generated comprehensive in situ Hi-C maps of DNA loops in human monocytes and differentiated macrophages. We demonstrate that dynamic looping events are regulatory rather than structural in nature and uncover widespread coordination of dynamic enhancer activity at preformed and acquired DNA loops. Enhancer-bound loop formation and enhancer activation of preformed loops together form multi-loop activation hubs at key macrophage genes. Activation hubs connect 3.4 enhancers per promoter and exhibit a strong enrichment for activator protein 1 (AP-1)-binding events, suggesting that multi-loop activation hubs involving cell-type-specific transcription factors represent an important class of regulatory chromatin structures for the spatiotemporal control of transcription.
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