期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 111, 期 21, 页码 E2191-E2199出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1320308111
关键词
chromatin interaction; genomics; bioinformatics; gene regulation; 3C
资金
- National Institutes of Health [HG006130]
Enhancer mapping has been greatly facilitated by various genomic marks associated with it. However, little is available in our tool-box 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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