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bioRxiv · 10.1101/183988

Temporal epigenomic profiling identifies AHR as dynamic super-enhancer controlled regulator of mesenchymal multipotency

Gerard, D.·Schmidt, F.·Ginolhac, A.·Schmitz, M.·Halder, R.·Ebert, P.·Schulz, M. H.·Sauter, T.·Sinkkonen, L.
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Abstract

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.

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Gerard, D., Schmidt, F., Ginolhac, A., Schmitz, M., Halder, R., Ebert, P., Schulz, M. H., Sauter, T., Sinkkonen, L.. 2017-09-03. Temporal epigenomic profiling identifies AHR as dynamic super-enhancer controlled regulator of mesenchymal multipotency. https://doi.org/10.1101/183988

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