Static and Dynamic DNA Loops form AP-1-Bound Activation Hubs during Macrophage Development

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 tran...

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Bibliographic Details
Published in:Molecular cell Vol. 67; no. 6; p. 1037
Main Authors: Phanstiel, Douglas H, Van Bortle, Kevin, Spacek, Damek, Hess, Gaelen T, Shamim, Muhammad Saad, Machol, Ido, Love, Michael I, Aiden, Erez Lieberman, Bassik, Michael C, Snyder, Michael P
Format: Journal Article
Language:English
Published: United States 21.09.2017
Subjects:
Binding Sites
Cell Differentiation
Cell Line, Tumor
Chromatin - chemistry
Chromatin - genetics
Chromatin - metabolism
Chromatin Assembly and Disassembly
DNA - chemistry
DNA - genetics
DNA - metabolism
Enhancer Elements, Genetic
Gene Expression Regulation
High-Throughput Nucleotide Sequencing
Humans
Macrophages - metabolism
Nucleic Acid Conformation
Phenotype
Protein Binding
Time Factors
Transcription Factor AP-1 - genetics
Transcription Factor AP-1 - metabolism
Transcription, Genetic
CTCF
cellular differentiation
DNA looping
Hi-C
AP-1
ISSN:1097-4164, 1097-4164
Online Access:Get more information
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Summary: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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ISSN:1097-4164
1097-4164
DOI:10.1016/j.molcel.2017.08.006