Reference : Temporal enhancer profiling of parallel lineages identifies AHR and GLIS1 as regulato...
Scientific journals : Article
Life sciences : Biochemistry, biophysics & molecular biology
Systems Biomedicine
http://hdl.handle.net/10993/38244
Temporal enhancer profiling of parallel lineages identifies AHR and GLIS1 as regulators of mesenchymal multipotency
English
Gerard, Déborah mailto [University of Luxembourg > Faculty of Science, Technology and Communication (FSTC) > Computer Science and Communications Research Unit (CSC) >]
Schmidt, Florian []
Ginolhac, Aurélien mailto [University of Luxembourg > Faculty of Science, Technology and Communication (FSTC) > Life Science Research Unit >]
Schmitz, Martine mailto [University of Luxembourg > Faculty of Science, Technology and Communication (FSTC) > Life Science Research Unit >]
Halder, Rashi mailto [University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > >]
Ebert, Peter []
Schulz, Marcel [Goethe University > Institute for Cardiovascular Research]
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 >]
14-Dec-2018
Nucleic Acids Research
Oxford University Press
Yes (verified by ORBilu)
International
0305-1048
1362-4962
Oxford
United Kingdom
[en] Temporal data on gene expression and context-specific open chromatin states can improve identification of key transcription factors (TFs) and the gene regulatory networks (GRNs) controlling cellular differentiation. However, their integration remains challenging. Here, we delineate a general approach for data-driven and unbiased identification of key TFs and dynamic GRNs, called EPIC-DREM. We generated time-series transcriptomic and epigenomic profiles during differentiation of mouse multipotent bone marrow stromal cell line (ST2) toward adipocytes and osteoblasts. Using our novel approach we constructed time-resolved GRNs for both lineages and identifed the shared TFs involved in both differentiation processes. To take an alternative approach to prioritize the identified shared regulators, we mapped dynamic super-enhancers in both lineages and associated them to target genes with correlated expression profiles. The combination of the two approaches identified aryl hydrocarbon receptor (AHR) and Glis family zinc finger 1 (GLIS1) as mesenchymal key TFs controlled by dynamic cell type-specific super-enhancers that become repressed in both lineages. AHR and GLIS1 control differentiation-induced genes and their overexpression can inhibit the lineage commitment of the multipotent bone marrow-derived ST2 cells.
University of Luxembourg: High Performance Computing - ULHPC
Fonds National de la Recherche - FnR ; University of Luxembourg - UL
http://hdl.handle.net/10993/38244
10.1093/nar/gky1240
https://academic.oup.com/nar/advance-article/doi/10.1093/nar/gky1240/5245443
The original publication is available at https://academic.oup.com/nar/advance-article/doi/10.1093/nar/gky1240/5245443

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