Global view of enhancer-promoter interactome in human cells

Enhancer mapping has been greatly facilitated by various genomic marks associated with it. However, little is available in our toolbox to link enhancers with their target promoters, hampering mechanistic understanding of enhancer-promoter (EP) interaction. We develop and characterize multiple genomi...

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Veröffentlicht in:Proceedings of the National Academy of Sciences - PNAS Jg. 111; H. 21; S. E2191
Hauptverfasser: He, Bing, Chen, Changya, Teng, Li, Tan, Kai
Format: Journal Article
Sprache:Englisch
Veröffentlicht: United States 27.05.2014
Schlagworte:
Cell Cycle Proteins - metabolism
Chromosomal Proteins, Non-Histone - metabolism
Cohesins
Computational Biology
Computer Simulation
Enhancer Elements, Genetic - genetics
Enhancer Elements, Genetic - physiology
Gene Expression Regulation - genetics
Gene Expression Regulation - physiology
Genomics - methods
Humans
Models, Genetic
Promoter Regions, Genetic - genetics
Promoter Regions, Genetic - physiology
Signal Transduction - physiology
3C
genomics
chromatin interaction
gene regulation
bioinformatics
ISSN:1091-6490, 1091-6490
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Zusammenfassung:Enhancer mapping has been greatly facilitated by various genomic marks associated with it. However, little is available in our toolbox to link enhancers with their target promoters, hampering mechanistic understanding of enhancer-promoter (EP) interaction. We develop and characterize multiple genomic features for distinguishing true EP pairs from noninteracting pairs. We integrate these features into a probabilistic predictor for EP interactions. Multiple validation experiments demonstrate a significant improvement over state-of-the-art approaches. Systematic analyses of EP interactions across 12 cell types reveal several global features of EP interactions: (i) a larger fraction of EP interactions are cell type specific than enhancers; (ii) promoters controlled by multiple enhancers have higher tissue specificity, but the regulating enhancers are less conserved; (iii) cohesin plays a role in mediating tissue-specific EP interactions via chromatin looping in a CTCF-independent manner. Our approach presents a systematic and effective strategy to decipher the mechanisms underlying EP communication.
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ISSN:1091-6490
1091-6490
DOI:10.1073/pnas.1320308111