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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 (Shh), which plays a pivotal role in the proliferation, differentiation and survival of neural progenitor cells both in...

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Autores principales: Benabdallah, Nezha S., Gautier, Philippe, Hekimoglu-Balkan, Betul, Lettice, Laura A., Bhatia, Shipra, Bickmore, Wendy A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Royal Society 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5133441/
https://www.ncbi.nlm.nih.gov/pubmed/27852806
http://dx.doi.org/10.1098/rsob.160197
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author Benabdallah, Nezha S.
Gautier, Philippe
Hekimoglu-Balkan, Betul
Lettice, Laura A.
Bhatia, Shipra
Bickmore, Wendy A.
author_facet Benabdallah, Nezha S.
Gautier, Philippe
Hekimoglu-Balkan, Betul
Lettice, Laura A.
Bhatia, Shipra
Bickmore, Wendy A.
author_sort Benabdallah, Nezha S.
collection PubMed
description 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.
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spelling pubmed-51334412016-12-12 SBE6: a novel long-range enhancer involved in driving sonic hedgehog expression in neural progenitor cells Benabdallah, Nezha S. Gautier, Philippe Hekimoglu-Balkan, Betul Lettice, Laura A. Bhatia, Shipra Bickmore, Wendy A. Open Biol Research 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. The Royal Society 2016-11-16 /pmc/articles/PMC5133441/ /pubmed/27852806 http://dx.doi.org/10.1098/rsob.160197 Text en © 2016 The Authors. http://creativecommons.org/licenses/by/4.0/ Published by the Royal Society under the terms of the Creative Commons Attribution License http://creativecommons.org/licenses/by/4.0/, which permits unrestricted use, provided the original author and source are credited.
spellingShingle Research
Benabdallah, Nezha S.
Gautier, Philippe
Hekimoglu-Balkan, Betul
Lettice, Laura A.
Bhatia, Shipra
Bickmore, Wendy A.
SBE6: a novel long-range enhancer involved in driving sonic hedgehog expression in neural progenitor cells
title SBE6: a novel long-range enhancer involved in driving sonic hedgehog expression in neural progenitor cells
title_full SBE6: a novel long-range enhancer involved in driving sonic hedgehog expression in neural progenitor cells
title_fullStr SBE6: a novel long-range enhancer involved in driving sonic hedgehog expression in neural progenitor cells
title_full_unstemmed SBE6: a novel long-range enhancer involved in driving sonic hedgehog expression in neural progenitor cells
title_short SBE6: a novel long-range enhancer involved in driving sonic hedgehog expression in neural progenitor cells
title_sort sbe6: a novel long-range enhancer involved in driving sonic hedgehog expression in neural progenitor cells
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5133441/
https://www.ncbi.nlm.nih.gov/pubmed/27852806
http://dx.doi.org/10.1098/rsob.160197
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