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

Diamanti, Klev (author)
Uppsala universitet,Beräkningsbiologi och bioinformatik
Umer, Husen M. (author)
Uppsala universitet,Beräkningsbiologi och bioinformatik
Kruczyk, Marcin (author)
Uppsala universitet,Beräkningsbiologi och bioinformatik
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Dabrowski, Michal J. (author)
Polish Acad Sci, Inst Comp Sci, PL-01248 Warsaw, Poland.
Cavalli, Marco (author)
Uppsala universitet,Medicinsk genetik och genomik,Science for Life Laboratory, SciLifeLab
Wadelius, Claes (author)
Uppsala universitet,Medicinsk genetik och genomik,Science for Life Laboratory, SciLifeLab
Komorowski, Jan (author)
Uppsala universitet,Science for Life Laboratory, SciLifeLab,Beräkningsbiologi och bioinformatik,Polish Acad Sci, Inst Comp Sci, PL-01248 Warsaw, Poland.
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 (creator_code:org_t)
2016-09-12
2016
English.
In: Nucleic Acids Research. - : Oxford University Press (OUP). - 0305-1048 .- 1362-4962. ; 44:19, s. 9110-9120
  • Journal article (peer-reviewed)
Abstract Subject headings
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  • 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 similar to 144k putative regulatory regions among the human cell-lines, with the majority of them being similar to 300 bp. We found similar to 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.

Subject headings

NATURVETENSKAP  -- Biologi -- Biokemi och molekylärbiologi (hsv//swe)
NATURAL SCIENCES  -- Biological Sciences -- Biochemistry and Molecular Biology (hsv//eng)

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