Models of human core transcriptional regulatory circuitries
- Violaine Saint-André1,5,
- Alexander J. Federation2,5,
- Charles Y. Lin2,
- Brian J. Abraham1,
- Jessica Reddy1,3,
- Tong Ihn Lee1,
- James E. Bradner2,4 and
- Richard A. Young1,3
- 1Whitehead Institute for Biomedical Research, Cambridge, Massachusetts 02142, USA;
- 2Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts 02215, USA;
- 3Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA;
- 4Department of Medicine, Harvard Medical School, Boston, Massachusetts 02115, USA
- Corresponding authors: young{at}wi.mit.edu, violaine.saintandre{at}gmail.com, james_bradner{at}dfci.harvard.edu
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↵5 These authors contributed equally to this work.
Abstract
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.
Footnotes
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[Supplemental material is available for this article.]
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Article published online before print. Article, supplemental material, and publication date are at http://www.genome.org/cgi/doi/10.1101/gr.197590.115.
- Received August 1, 2015.
- Accepted December 21, 2015.
This article is distributed exclusively by Cold Spring Harbor Laboratory Press for the first six months after the full-issue publication date (see http://genome.cshlp.org/site/misc/terms.xhtml). After six months, it is available under a Creative Commons License (Attribution-NonCommercial 4.0 International), as described at http://creativecommons.org/licenses/by-nc/4.0/.
