PT - JOURNAL ARTICLE AU - Deborah Gérard AU - Florian Schmidt AU - Aurélien Ginolhac AU - Martine Schmitz AU - Rashi Halder AU - Peter Ebert AU - Marcel H. Schulz AU - Thomas Sauter AU - Lasse Sinkkonen TI - Temporal epigenomic profiling identifies AHR and GLIS1 as super-enhancer controlled regulators of mesenchymal multipotency AID - 10.1101/183988 DP - 2018 Jan 01 TA - bioRxiv PG - 183988 4099 - http://biorxiv.org/content/early/2018/03/26/183988.short 4100 - http://biorxiv.org/content/early/2018/03/26/183988.full AB - 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 cells (MSCs) towards adipocytes and osteoblasts. Using our novel approach we constructed time-resolved GRNs for both lineages. To prioritize the identified shared regulators, we mapped dynamic super-enhancers in both lineages and associated them to target genes with correlated expression profiles. We identified aryl hydrocarbon receptor (AHR) and Glis family zinc finger 1 (GLIS1) as mesenchymal key TFs controlled by dynamic MSC-specific super-enhancers that become repressed in both lineages. AHR and GLIS1 control differentiation-induced genes and we propose they function as guardians of mesenchymal multipotency.