title: SBE6: a novel long-range enhancer involved in driving sonic hedgehog expression in neural progenitor cells.
abstract: The expression of genes with key roles in development is under very tight spatial and temporal control, mediated by enhancers. A classic example of this is the sonic hedgehog gene (Shh), which plays a pivotal role in the proliferation, differentiation and survival of neural progenitor cells both in vivo and in vitro. Shh expression in the brain is tightly controlled by several known enhancers that have been identified through genetic, genomic and functional assays. Using chromatin profiling during the differentiation of embryonic stem cells to neural progenitor cells, here we report the identification of a novel long-range enhancer for Shh-Shh-brain-enhancer-6 (SBE6)-that is located 100 kb upstream of Shh and that is required for the proper induction of Shh expression during this differentiation programme. This element is capable of driving expression in the vertebrate brain. Our study illustrates how a chromatin-focused approach, coupled to in vivo testing, can be used to identify new cell-type specific cis-regulatory elements, and points to yet further complexity in the control of Shh expression during embryonic brain development.
authors.affiliation: MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Crewe Road, Edinburgh EH4 2XU, UK.|Edinburgh Super Resolution Imaging Consortium (ESRIC), Institute of Genetics and Molecular Medicine, University of Edinburgh, Crewe Road, Edinburgh EH4 2XU, UK.
authors.forename: Nezha S
authors.initials: NS
authors.lastname: Benabdallah
authors.affiliation: MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Crewe Road, Edinburgh EH4 2XU, UK.
authors.forename: Philippe
authors.initials: P
authors.lastname: Gautier
authors.affiliation: MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Crewe Road, Edinburgh EH4 2XU, UK.
authors.forename: Betul
authors.initials: B
authors.lastname: Hekimoglu-Balkan
authors.affiliation: MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Crewe Road, Edinburgh EH4 2XU, UK.
authors.forename: Laura A
authors.initials: LA
authors.lastname: Lettice
authors.affiliation: MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Crewe Road, Edinburgh EH4 2XU, UK.
authors.forename: Shipra
authors.initials: S
authors.lastname: Bhatia
authors.affiliation: MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Crewe Road, Edinburgh EH4 2XU, UK wendy.bickmore@igmm.ed.ac.uk.
authors.forename: Wendy A
authors.identifier: 0000-0001-6660-7735
authors.initials: WA
authors.lastname: Bickmore
mesh_terms: D000818:Animals; D001921:Brain / Q000196:embryology*; D002454:Cell Differentiation; D002843:Chromatin / Q000235:genetics; D004742:Enhancer Elements, Genetic; D020869:Gene Expression Profiling / Q000379:methods*; D018507:Gene Expression Regulation, Developmental; D053823:Hedgehog Proteins / Q000235:genetics*; D000066449:Human Embryonic Stem Cells / Q000166:cytology*; D006801:Humans; D051379:Mice; D015398:Signal Transduction
chemical_list: D002843:Chromatin; D053823:Hedgehog Proteins; C465570:Shh protein, mouse
keywords: long-range enhancer; neural progenitor cells; sonic hedgehog