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Static and Dynamic DNA Loops form AP-1-Bound Activation Hubs during Macrophage Development
Douglas H Phanstiel1, Kevin Van Bortle2, Damek Spacek2
1Department of Cell Biology and Physiology, University of North Carolina, Chapel Hill, NC 27599, USA; Thurston Arthritis Research Center, University of North Carolina, Chapel Hill, NC 27599, USA; Department of Genetics, Stanford University, Stanford, CA 94305, USA.
Molecular Cell
|September 12, 2017
Summary
Dynamic DNA loops in human cells regulate gene transcription during differentiation. These regulatory loops form activation hubs, connecting enhancers to promoters, especially for macrophage genes, and are crucial for cell-specific gene control.
Area of Science:
- Genomics
- Molecular Biology
- Epigenetics
Background:
- The 3D genome structure involves chromatin loops regulating gene transcription.
- Understanding dynamic chromatin structure during cell differentiation is key.
Purpose of the Study:
- To investigate the mechanisms of context-specific 3D chromatin structure and transcription during cellular differentiation.
- To analyze dynamic looping events and their regulatory roles.
Main Methods:
- Generated in situ Hi-C maps of DNA loops in human monocytes and differentiated macrophages.
- Analyzed dynamic looping events and enhancer activity coordination.
Main Results:
- Demonstrated that dynamic looping events are primarily regulatory, not structural.
- Uncovered coordinated dynamic enhancer activity at DNA loops.
- Identified multi-loop activation hubs connecting multiple enhancers to promoters at key macrophage genes.
- Found enrichment for activator protein 1 (AP-1) binding events in these hubs.
Conclusions:
- Dynamic DNA loops play a regulatory role in gene transcription during cell differentiation.
- Multi-loop activation hubs, involving cell-type-specific transcription factors like AP-1, are critical for spatiotemporal control of transcription.
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