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Nucleic Acids Res. 2011 Apr;39(7):2492-502. doi: 10.1093/nar/gkq1081. Epub 2010 Nov 24.

Integrative analysis of genomic, functional and protein interaction data predicts long-range enhancer-target gene interactions.

Author information

  • 1Berlin-Brandenburg Center for Regenerative Therapies, Charité-Universitätsmedizin Berlin, Max Planck Institute for Molecular Genetics, Berlin, Germany.

Abstract

Multicellular organismal development is controlled by a complex network of transcription factors, promoters and enhancers. Although reliable computational and experimental methods exist for enhancer detection, prediction of their target genes remains a major challenge. On the basis of available literature and ChIP-seq and ChIP-chip data for enhanceosome factor p300 and the transcriptional regulator Gli3, we found that genomic proximity and conserved synteny predict target genes with a relatively low recall of 12-27% within 2 Mb intervals centered at the enhancers. Here, we show that functional similarities between enhancer binding proteins and their transcriptional targets and proximity in the protein-protein interactome improve prediction of target genes. We used all four features to train random forest classifiers that predict target genes with a recall of 58% in 2 Mb intervals that may contain dozens of genes, representing a better than two-fold improvement over the performance of prediction based on single features alone. Genome-wide ChIP data is still relatively poorly understood, and it remains difficult to assign biological significance to binding events. Our study represents a first step in integrating various genomic features in order to elucidate the genomic network of long-range regulatory interactions.

PMID:
21109530
[PubMed - indexed for MEDLINE]
PMCID:
PMC3074119
Free PMC Article

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