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Sox2-Dependent 3D Chromatin Interactomes in Transcription, Neural Stem Cell Proliferation and Neurodevelopmental Diseases

In our article, we asked whether Sox2, a transcription factor important in brain development and disease, is involved in gene regulation through its action on long-range interactions between promoters and distant enhancers. Our findings highlight that Sox2 shapes a genome-wide network of promoter-en...

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Detalles Bibliográficos
Autores principales: Wei, Chia-Lin, Nicolis, Silvia K, Zhu, Yanfen, Pagin, Miriam
Formato: Online Artículo Texto
Lenguaje:English
Publicado: SAGE Publications 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6686325/
https://www.ncbi.nlm.nih.gov/pubmed/31431802
http://dx.doi.org/10.1177/1179069519868224
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author Wei, Chia-Lin
Nicolis, Silvia K
Zhu, Yanfen
Pagin, Miriam
author_facet Wei, Chia-Lin
Nicolis, Silvia K
Zhu, Yanfen
Pagin, Miriam
author_sort Wei, Chia-Lin
collection PubMed
description In our article, we asked whether Sox2, a transcription factor important in brain development and disease, is involved in gene regulation through its action on long-range interactions between promoters and distant enhancers. Our findings highlight that Sox2 shapes a genome-wide network of promoter-enhancer interactions, acting by direct binding to these elements. Sox2 loss affects the three-dimensional (3D) genome and decreases the activity of a subset of genes involved in Sox2-bound interactions. At least one of such downregulated genes, Socs3, is critical for long-term neural stem cell maintenance. These results point to the possibility of identifying a transcriptional network downstream to Sox2, and involved in neural stem cell maintenance. In addition, interacting Sox2-bound enhancers are often connected to genes which are relevant, in man, to neurodevelopmental disease; this may facilitate the detection of functionally relevant mutations in regulatory elements in man, contributing to neural disease.
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spelling pubmed-66863252019-08-20 Sox2-Dependent 3D Chromatin Interactomes in Transcription, Neural Stem Cell Proliferation and Neurodevelopmental Diseases Wei, Chia-Lin Nicolis, Silvia K Zhu, Yanfen Pagin, Miriam J Exp Neurosci Commentary In our article, we asked whether Sox2, a transcription factor important in brain development and disease, is involved in gene regulation through its action on long-range interactions between promoters and distant enhancers. Our findings highlight that Sox2 shapes a genome-wide network of promoter-enhancer interactions, acting by direct binding to these elements. Sox2 loss affects the three-dimensional (3D) genome and decreases the activity of a subset of genes involved in Sox2-bound interactions. At least one of such downregulated genes, Socs3, is critical for long-term neural stem cell maintenance. These results point to the possibility of identifying a transcriptional network downstream to Sox2, and involved in neural stem cell maintenance. In addition, interacting Sox2-bound enhancers are often connected to genes which are relevant, in man, to neurodevelopmental disease; this may facilitate the detection of functionally relevant mutations in regulatory elements in man, contributing to neural disease. SAGE Publications 2019-08-07 /pmc/articles/PMC6686325/ /pubmed/31431802 http://dx.doi.org/10.1177/1179069519868224 Text en © The Author(s) 2019 http://www.creativecommons.org/licenses/by-nc/4.0/ This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License (http://www.creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages (https://us.sagepub.com/en-us/nam/open-access-at-sage).
spellingShingle Commentary
Wei, Chia-Lin
Nicolis, Silvia K
Zhu, Yanfen
Pagin, Miriam
Sox2-Dependent 3D Chromatin Interactomes in Transcription, Neural Stem Cell Proliferation and Neurodevelopmental Diseases
title Sox2-Dependent 3D Chromatin Interactomes in Transcription, Neural Stem Cell Proliferation and Neurodevelopmental Diseases
title_full Sox2-Dependent 3D Chromatin Interactomes in Transcription, Neural Stem Cell Proliferation and Neurodevelopmental Diseases
title_fullStr Sox2-Dependent 3D Chromatin Interactomes in Transcription, Neural Stem Cell Proliferation and Neurodevelopmental Diseases
title_full_unstemmed Sox2-Dependent 3D Chromatin Interactomes in Transcription, Neural Stem Cell Proliferation and Neurodevelopmental Diseases
title_short Sox2-Dependent 3D Chromatin Interactomes in Transcription, Neural Stem Cell Proliferation and Neurodevelopmental Diseases
title_sort sox2-dependent 3d chromatin interactomes in transcription, neural stem cell proliferation and neurodevelopmental diseases
topic Commentary
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6686325/
https://www.ncbi.nlm.nih.gov/pubmed/31431802
http://dx.doi.org/10.1177/1179069519868224
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