Maps of context-dependent putative regulatory regions and genomic signal interactions

Nucleic Acids Res. 2016 Nov 2;44(19):9110-9120. doi: 10.1093/nar/gkw800. Epub 2016 Sep 12.


Gene transcription is regulated mainly by transcription factors (TFs). ENCODE and Roadmap Epigenomics provide global binding profiles of TFs, which can be used to identify regulatory regions. To this end we implemented a method to systematically construct cell-type and species-specific maps of regulatory regions and TF-TF interactions. We illustrated the approach by developing maps for five human cell-lines and two other species. We detected ∼144k putative regulatory regions among the human cell-lines, with the majority of them being ∼300 bp. We found ∼20k putative regulatory elements in the ENCODE heterochromatic domains suggesting a large regulatory potential in the regions presumed transcriptionally silent. Among the most significant TF interactions identified in the heterochromatic regions were CTCF and the cohesin complex, which is in agreement with previous reports. Finally, we investigated the enrichment of the obtained putative regulatory regions in the 3D chromatin domains. More than 90% of the regions were discovered in the 3D contacting domains. We found a significant enrichment of GWAS SNPs in the putative regulatory regions. These significant enrichments provide evidence that the regulatory regions play a crucial role in the genomic structural stability. Additionally, we generated maps of putative regulatory regions for prostate and colorectal cancer human cell-lines.

MeSH terms

  • Binding Sites
  • Cell Line
  • Chromatin / genetics
  • Chromatin / metabolism
  • Chromatin Immunoprecipitation
  • Chromosome Mapping
  • Computational Biology / methods
  • Genome, Human
  • Genome-Wide Association Study
  • Genomics* / methods
  • High-Throughput Nucleotide Sequencing
  • Humans
  • Molecular Sequence Annotation
  • Polymorphism, Single Nucleotide
  • Protein Binding
  • Protein Interaction Mapping
  • Protein Interaction Maps
  • Regulatory Sequences, Nucleic Acid*
  • Transcription Factors / metabolism


  • Chromatin
  • Transcription Factors