SBE6, a novel long-range enhancer involved in driving Sonic Hedgehog expression in neural progenitor cells

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 (<i>Shh</i>) that plays a pivotal role in the proliferation, differentiation and survival of neural progenitor cells both <i>in vivo</i> and <i>in vitro. Shh</i> 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 <i>Shh</i> and that is required for the proper induction of <i>Shh</i> 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 <i>in vivo</i> testing, can be used to identify new cell-type specific <i>cis</i>-regulatory elements and points to yet further complexity in the control of <i>Shh</i> expression during embryonic brain development

Supplementary Figure 3 from SBE6: a novel long-range enhancer involved in driving sonic hedgehog expression in neural progenitor cells

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 (<i>Shh</i>) that plays a pivotal role in the proliferation, differentiation and survival of neural progenitor cells both <i>in vivo</i> and <i>in vitro. Shh</i> 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 <i>Shh</i> and that is required for the proper induction of <i>Shh</i> 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 <i>in vivo</i> testing, can be used to identify new cell-type specific <i>cis</i>-regulatory elements and points to yet further complexity in the control of <i>Shh</i> expression during embryonic brain development

Supplementary Figure 1 from SBE6: a novel long-range enhancer involved in driving sonic hedgehog expression in neural progenitor cells

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 (<i>Shh</i>) that plays a pivotal role in the proliferation, differentiation and survival of neural progenitor cells both <i>in vivo</i> and <i>in vitro. Shh</i> 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 <i>Shh</i> and that is required for the proper induction of <i>Shh</i> 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 <i>in vivo</i> testing, can be used to identify new cell-type specific <i>cis</i>-regulatory elements and points to yet further complexity in the control of <i>Shh</i> expression during embryonic brain development