Static and Dynamic DNA Loops form AP-1-Bound Activation Hubs during Macrophage Development
Autor: | Michael I. Love, Damek V. Spacek, Gaelen T. Hess, Douglas H. Phanstiel, Muhammad S. Shamim, Kevin Van Bortle, Erez Lieberman Aiden, Michael C. Bassik, Michael Snyder, Ido Machol |
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Rok vydání: | 2017 |
Předmět: |
0301 basic medicine
Time Factors Transcription Genetic Cellular differentiation Biology Article 03 medical and health sciences chemistry.chemical_compound Transcription (biology) Cell Line Tumor Humans Enhancer Molecular Biology Gene Transcription factor Genetics Binding Sites Macrophages High-Throughput Nucleotide Sequencing Cell Differentiation Cell Biology DNA Chromatin Assembly and Disassembly Chromatin Cell biology Transcription Factor AP-1 030104 developmental biology Enhancer Elements Genetic Phenotype chemistry Gene Expression Regulation CTCF Nucleic Acid Conformation Protein Binding |
Zdroj: | Molecular cell. 67(6) |
ISSN: | 1097-4164 |
Popis: | 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. |
Databáze: | OpenAIRE |
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