title: Models of human core transcriptional regulatory circuitries.
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.
authors: Whitehead Institute for Biomedical Research, Cambridge, Massachusetts 02142, USA;
authors: Violaine
authors: V
authors: Saint-André
authors: Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts 02215, USA;
authors: Alexander J
authors: AJ
authors: Federation
authors: Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts 02215, USA;
authors: Charles Y
authors: CY
authors: Lin
authors: Whitehead Institute for Biomedical Research, Cambridge, Massachusetts 02142, USA;
authors: Brian J
authors: BJ
authors: Abraham
authors: Whitehead Institute for Biomedical Research, Cambridge, Massachusetts 02142, USA; Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA;
authors: Jessica
authors: J
authors: Reddy
authors: Whitehead Institute for Biomedical Research, Cambridge, Massachusetts 02142, USA;
authors: Tong Ihn
authors: TI
authors: Lee
authors: Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts 02215, USA; Department of Medicine, Harvard Medical School, Boston, Massachusetts 02115, USA.
authors: James E
authors: JE
authors: Bradner
authors: Whitehead Institute for Biomedical Research, Cambridge, Massachusetts 02142, USA; Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA;
authors: Richard A
authors: RA
authors: Young
mesh_terms: D001665:Binding Sites; D002460:Cell Line; D005786:Gene Expression Regulation; D053263:Gene Regulatory Networks; D000066449:Human Embryonic Stem Cells; D006801:Humans; D009928:Organ Specificity; D011485:Protein Binding; D014157:Transcription Factors / Q000378:metabolism*; D014158:Transcription, Genetic
chemical_list: D014157:Transcription Factors