Reference : Cell type-selective disease-association of genes under high regulatory load
Scientific journals : Article
Life sciences : Biochemistry, biophysics & molecular biology
http://hdl.handle.net/10993/21893
Cell type-selective disease-association of genes under high regulatory load
English
Galhardo, Mafalda Sofia mailto [University of Luxembourg > Faculty of Science, Technology and Communication (FSTC) > Life Science Research Unit >]
Berninger, Philipp mailto [University of Basel > Biozentrum]
Nguyen, Thanh Phuong mailto [University of Luxembourg > Faculty of Science, Technology and Communication (FSTC) > Life Science Research Unit >]
Sauter, Thomas mailto [University of Luxembourg > Faculty of Science, Technology and Communication (FSTC) > Life Science Research Unit >]
Sinkkonen, Lasse mailto [University of Luxembourg > Faculty of Science, Technology and Communication (FSTC) > Life Science Research Unit >]
3-Sep-2015
Nucleic Acids Research
Oxford University Press
43
18
8839-8855
Yes (verified by ORBilu)
International
0305-1048
1362-4962
Oxford
United Kingdom
[en] high regulatory load ; epigenomics ; active enhancer ; disease-association ; microRNA ; transcription factor
[en] We previously showed that disease-linked metabolic genes are often under combinatorial regulation. Using the genome-wide ChIP-Seq binding profiles for 93 transcription factors in nine different cell lines, we show that genes under high regulatory load are significantly enriched for disease-association across cell types. We find that transcription factor load correlates with the enhancer load of the genes and thereby allows the identification of genes under high regulatory load by epigenomic mapping of active enhancers. Identification of the high enhancer load genes across 139 samples from 96 different cell and tissue types reveals a consistent enrichment for disease-associated genes in a cell type-selective manner. The underlying genes are not limited to super-enhancer genes and show several types of disease-association evidence beyond genetic variation (such as biomarkers). Interestingly, the high regulatory load genes are involved in more KEGG pathways than expected by chance, exhibit increased betweenness centrality in the interaction network of liver disease genes, and carry longer 3'UTRs with more microRNA (miRNA) binding sites than genes on average, suggesting a role as hubs integrating signals within regulatory networks. In summary, epigenetic mapping of active enhancers presents a promising and unbiased approach for identification of novel disease genes in a cell type-selective manner.
University of Luxembourg: High Performance Computing - ULHPC
Fonds National de la Recherche - FnR
Researchers ; Professionals
http://hdl.handle.net/10993/21893
10.1093/nar/gkv863
http://nar.oxfordjournals.org/content/early/2015/09/03/nar.gkv863.full
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.

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