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Cornelia de Lange syndrome mutations in NIPBL can impair cohesin-mediated DNA loop extrusion
Cornelia de Lange syndrome (CdLS) is a developmental multisystem disorder frequently associated with mutations in NIPBL. CdLS is thought to arise from developmental gene regulation defects, but how NIPBL mutations cause these is unknown. Here we show that several NIPBL mutations impair the DNA loop...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
National Academy of Sciences
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9170158/ https://www.ncbi.nlm.nih.gov/pubmed/35476527 http://dx.doi.org/10.1073/pnas.2201029119 |
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author | Panarotto, Melanie Davidson, Iain F. Litos, Gabriele Schleiffer, Alexander Peters, Jan-Michael |
author_facet | Panarotto, Melanie Davidson, Iain F. Litos, Gabriele Schleiffer, Alexander Peters, Jan-Michael |
author_sort | Panarotto, Melanie |
collection | PubMed |
description | Cornelia de Lange syndrome (CdLS) is a developmental multisystem disorder frequently associated with mutations in NIPBL. CdLS is thought to arise from developmental gene regulation defects, but how NIPBL mutations cause these is unknown. Here we show that several NIPBL mutations impair the DNA loop extrusion activity of cohesin. Because this activity is required for the formation of chromatin loops and topologically associating domains, which have important roles in gene regulation, our results suggest that defects in cohesin-mediated loop extrusion contribute to the etiology of CdLS by altering interactions between developmental genes and their enhancers. |
format | Online Article Text |
id | pubmed-9170158 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | National Academy of Sciences |
record_format | MEDLINE/PubMed |
spelling | pubmed-91701582022-06-07 Cornelia de Lange syndrome mutations in NIPBL can impair cohesin-mediated DNA loop extrusion Panarotto, Melanie Davidson, Iain F. Litos, Gabriele Schleiffer, Alexander Peters, Jan-Michael Proc Natl Acad Sci U S A Biological Sciences Cornelia de Lange syndrome (CdLS) is a developmental multisystem disorder frequently associated with mutations in NIPBL. CdLS is thought to arise from developmental gene regulation defects, but how NIPBL mutations cause these is unknown. Here we show that several NIPBL mutations impair the DNA loop extrusion activity of cohesin. Because this activity is required for the formation of chromatin loops and topologically associating domains, which have important roles in gene regulation, our results suggest that defects in cohesin-mediated loop extrusion contribute to the etiology of CdLS by altering interactions between developmental genes and their enhancers. National Academy of Sciences 2022-04-27 2022-05-03 /pmc/articles/PMC9170158/ /pubmed/35476527 http://dx.doi.org/10.1073/pnas.2201029119 Text en Copyright © 2022 the Author(s). Published by PNAS. https://creativecommons.org/licenses/by/4.0/This open access article is distributed under Creative Commons Attribution License 4.0 (CC BY) (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Biological Sciences Panarotto, Melanie Davidson, Iain F. Litos, Gabriele Schleiffer, Alexander Peters, Jan-Michael Cornelia de Lange syndrome mutations in NIPBL can impair cohesin-mediated DNA loop extrusion |
title | Cornelia de Lange syndrome mutations in NIPBL can impair cohesin-mediated DNA loop extrusion |
title_full | Cornelia de Lange syndrome mutations in NIPBL can impair cohesin-mediated DNA loop extrusion |
title_fullStr | Cornelia de Lange syndrome mutations in NIPBL can impair cohesin-mediated DNA loop extrusion |
title_full_unstemmed | Cornelia de Lange syndrome mutations in NIPBL can impair cohesin-mediated DNA loop extrusion |
title_short | Cornelia de Lange syndrome mutations in NIPBL can impair cohesin-mediated DNA loop extrusion |
title_sort | cornelia de lange syndrome mutations in nipbl can impair cohesin-mediated dna loop extrusion |
topic | Biological Sciences |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9170158/ https://www.ncbi.nlm.nih.gov/pubmed/35476527 http://dx.doi.org/10.1073/pnas.2201029119 |
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