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Transcription factor Sox10 orchestrates activity of a neural crest-specific enhancer in the vicinity of its gene
The Sox10 transcription factor is a central regulator of vertebrate neural crest and nervous system development. Its expression is likely controlled by multiple enhancer elements, among them U3 (alternatively known as MCS4). Here we analyze U3 activity to obtain deeper insights into Sox10 function a...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2012
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3245941/ https://www.ncbi.nlm.nih.gov/pubmed/21908409 http://dx.doi.org/10.1093/nar/gkr734 |
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author | Wahlbuhl, Mandy Reiprich, Simone Vogl, Michael R. Bösl, Michael R. Wegner, Michael |
author_facet | Wahlbuhl, Mandy Reiprich, Simone Vogl, Michael R. Bösl, Michael R. Wegner, Michael |
author_sort | Wahlbuhl, Mandy |
collection | PubMed |
description | The Sox10 transcription factor is a central regulator of vertebrate neural crest and nervous system development. Its expression is likely controlled by multiple enhancer elements, among them U3 (alternatively known as MCS4). Here we analyze U3 activity to obtain deeper insights into Sox10 function and expression in the neural crest and its derivatives. U3 activity strongly depends on the presence of Sox10 that regulates its own expression as commonly observed for important developmental regulators. Sox10 bound directly as monomer to at least three sites in U3, whereas a fourth site preferred dimers. Deletion of these sites efficiently reduced U3 activity in transfected cells and transgenic mice. In stimulating the U3 enhancer, Sox10 synergized with many other transcription factors present in neural crest and developing peripheral nervous system including Pax3, FoxD3, AP2α, Krox20 and Sox2. In case of FoxD3, synergism involved Sox10-dependent recruitment to the U3 enhancer, while Sox10 and AP2α each had to bind to the regulatory region. Our study points to the importance of autoregulatory activity and synergistic interactions for maintenance of Sox10 expression and functional activity of Sox10 in the neural crest regulatory network. |
format | Online Article Text |
id | pubmed-3245941 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-32459412012-01-03 Transcription factor Sox10 orchestrates activity of a neural crest-specific enhancer in the vicinity of its gene Wahlbuhl, Mandy Reiprich, Simone Vogl, Michael R. Bösl, Michael R. Wegner, Michael Nucleic Acids Res Gene Regulation, Chromatin and Epigenetics The Sox10 transcription factor is a central regulator of vertebrate neural crest and nervous system development. Its expression is likely controlled by multiple enhancer elements, among them U3 (alternatively known as MCS4). Here we analyze U3 activity to obtain deeper insights into Sox10 function and expression in the neural crest and its derivatives. U3 activity strongly depends on the presence of Sox10 that regulates its own expression as commonly observed for important developmental regulators. Sox10 bound directly as monomer to at least three sites in U3, whereas a fourth site preferred dimers. Deletion of these sites efficiently reduced U3 activity in transfected cells and transgenic mice. In stimulating the U3 enhancer, Sox10 synergized with many other transcription factors present in neural crest and developing peripheral nervous system including Pax3, FoxD3, AP2α, Krox20 and Sox2. In case of FoxD3, synergism involved Sox10-dependent recruitment to the U3 enhancer, while Sox10 and AP2α each had to bind to the regulatory region. Our study points to the importance of autoregulatory activity and synergistic interactions for maintenance of Sox10 expression and functional activity of Sox10 in the neural crest regulatory network. Oxford University Press 2012-01 2011-09-09 /pmc/articles/PMC3245941/ /pubmed/21908409 http://dx.doi.org/10.1093/nar/gkr734 Text en © The Author(s) 2011. Published by Oxford University Press. http://creativecommons.org/licenses/by-nc/3.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Gene Regulation, Chromatin and Epigenetics Wahlbuhl, Mandy Reiprich, Simone Vogl, Michael R. Bösl, Michael R. Wegner, Michael Transcription factor Sox10 orchestrates activity of a neural crest-specific enhancer in the vicinity of its gene |
title | Transcription factor Sox10 orchestrates activity of a neural crest-specific enhancer in the vicinity of its gene |
title_full | Transcription factor Sox10 orchestrates activity of a neural crest-specific enhancer in the vicinity of its gene |
title_fullStr | Transcription factor Sox10 orchestrates activity of a neural crest-specific enhancer in the vicinity of its gene |
title_full_unstemmed | Transcription factor Sox10 orchestrates activity of a neural crest-specific enhancer in the vicinity of its gene |
title_short | Transcription factor Sox10 orchestrates activity of a neural crest-specific enhancer in the vicinity of its gene |
title_sort | transcription factor sox10 orchestrates activity of a neural crest-specific enhancer in the vicinity of its gene |
topic | Gene Regulation, Chromatin and Epigenetics |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3245941/ https://www.ncbi.nlm.nih.gov/pubmed/21908409 http://dx.doi.org/10.1093/nar/gkr734 |
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