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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...

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Autores principales: Panarotto, Melanie, Davidson, Iain F., Litos, Gabriele, Schleiffer, Alexander, Peters, Jan-Michael
Formato: Online Artículo Texto
Lenguaje:English
Publicado: National Academy of Sciences 2022
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.
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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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