Models of human core transcriptional regulatory circuitries

Violaine Saint-André (1) , Alexander Federation (2) , Charles Lin (2) , Brian Abraham (1) , Jessica Reddy (1, 3) , Tong Ihn Lee (1) , James E Bradner (2, 4) , Richard Young (1, 3)

1 Whitehead Institute
2 Dana-Farber Cancer Institute [Boston]
3 Department of Biology [MIT Cambridge, USA]
4 HMS - Harvard Medical School [Boston]

A small set of core transcription factors (TFs) dominates control of the gene expression program in embryonic stem cells and other well-studied cellular models. These core TFs collectively regulate their own gene expression, thus forming an interconnected auto-regulatory loop that can be considered the core transcriptional regulatory circuitry (CRC) for that cell type. There is limited knowledge of core TFs, and thus models of core regulatory circuitry, for most cell types. We recently discovered that genes encoding known core TFs forming CRCs are driven by super-enhancers, which provides an opportunity to systematically predict CRCs in poorly studied cell types through super-enhancer mapping. Here, we use super-enhancer maps to generate CRC models for 75 human cell and tissue types. These core circuitry models should prove valuable for further investigating cell-type-specific transcriptional regulation in healthy and diseased cells.

Domaines: Sciences du Vivant [q-bio]

Violaine Saint-André, Alexander Federation, Charles Lin, Brian Abraham, Jessica Reddy, et al.. Models of human core transcriptional regulatory circuitries. Genome Research, 2016, 26 (3), pp.385-396. ⟨10.1101/gr.197590.115⟩. ⟨pasteur-02871950⟩