Maps of context-dependent putative regulatory regions and genomic signal interactions.
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.
Department of Cell and Molecular Biology, Uppsala University, Uppsala SE-751-24, Sweden.
Klev
http://orcid.org/0000-0002-4922-8415
K
Diamanti
Department of Cell and Molecular Biology, Uppsala University, Uppsala SE-751-24, Sweden.
Husen M
HM
Umer
Department of Cell and Molecular Biology, Uppsala University, Uppsala SE-751-24, Sweden.
Marcin
M
Kruczyk
Science for Life Laboratory, Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala SE-751-08, Sweden.
Michał J
MJ
Dąbrowski
Institute of Computer Science, Polish Academy of Sciences, Warsaw 012-48, Poland.
Marco
M
Cavalli
Institute of Computer Science, Polish Academy of Sciences, Warsaw 012-48, Poland.
Claes
C
Wadelius
Department of Cell and Molecular Biology, Uppsala University, Uppsala SE-751-24, Sweden jan.komorowski@icm.uu.se.|Science for Life Laboratory, Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala SE-751-08, Sweden.
Jan
J
Komorowski
D001665:Binding Sites; D002460:Cell Line; D002843:Chromatin / Q000235:genetics / Q000378:metabolism; D047369:Chromatin Immunoprecipitation; D002874:Chromosome Mapping; D019295:Computational Biology / Q000379:methods; D015894:Genome, Human; D055106:Genome-Wide Association Study; D023281:Genomics / Q000379:methods; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D058977:Molecular Sequence Annotation; D020641:Polymorphism, Single Nucleotide; D011485:Protein Binding; D025941:Protein Interaction Mapping; D060066:Protein Interaction Maps; D012045:Regulatory Sequences, Nucleic Acid; D014157:Transcription Factors / Q000378:metabolism
D002843:Chromatin; D014157:Transcription Factors