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Profound alterations of the chromatin architecture at chromosome 11p15.5 in cells from Beckwith-Wiedemann and Silver-Russell syndromes patients

Beckwith-Wiedemann syndrome (BWS) and Silver-Russell syndrome (SRS) are imprinting-related disorders associated with genetic/epigenetic alterations of the 11p15.5 region, which harbours two clusters of imprinted genes (IGs). 11p15.5 IGs are regulated by the methylation status of imprinting control r...

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Autores principales: Rovina, Davide, La Vecchia, Marta, Cortesi, Alice, Fontana, Laura, Pesant, Matthieu, Maitz, Silvia, Tabano, Silvia, Bodega, Beatrice, Miozzo, Monica, Sirchia, Silvia M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7237657/
https://www.ncbi.nlm.nih.gov/pubmed/32427849
http://dx.doi.org/10.1038/s41598-020-65082-1
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author Rovina, Davide
La Vecchia, Marta
Cortesi, Alice
Fontana, Laura
Pesant, Matthieu
Maitz, Silvia
Tabano, Silvia
Bodega, Beatrice
Miozzo, Monica
Sirchia, Silvia M.
author_facet Rovina, Davide
La Vecchia, Marta
Cortesi, Alice
Fontana, Laura
Pesant, Matthieu
Maitz, Silvia
Tabano, Silvia
Bodega, Beatrice
Miozzo, Monica
Sirchia, Silvia M.
author_sort Rovina, Davide
collection PubMed
description Beckwith-Wiedemann syndrome (BWS) and Silver-Russell syndrome (SRS) are imprinting-related disorders associated with genetic/epigenetic alterations of the 11p15.5 region, which harbours two clusters of imprinted genes (IGs). 11p15.5 IGs are regulated by the methylation status of imprinting control regions ICR1 and ICR2. 3D chromatin structure is thought to play a pivotal role in gene expression control; however, chromatin architecture models are still poorly defined in most cases, particularly for IGs. Our study aimed at elucidating 11p15.5 3D structure, via 3C and 3D FISH analyses of cell lines derived from healthy, BWS or SRS children. We found that, in healthy cells, IGF2/H19 and CDKN1C/KCNQ1OT1 domains fold in complex chromatin conformations, that facilitate the control of IGs mediated by distant enhancers. In patient-derived cell lines, we observed a profound impairment of such a chromatin architecture. Specifically, we identified a cross-talk between IGF2/H19 and CDKN1C/KCNQ1OT1 domains, consisting in in cis, monoallelic interactions, that are present in healthy cells but lost in patient cell lines: an inter-domain association that sees ICR2 move close to IGF2 on one allele, and to H19 on the other. Moreover, an intra-domain association within the CDKN1C/KCNQ1OT1 locus seems to be crucial for maintaining the 3D organization of the region.
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spelling pubmed-72376572020-05-29 Profound alterations of the chromatin architecture at chromosome 11p15.5 in cells from Beckwith-Wiedemann and Silver-Russell syndromes patients Rovina, Davide La Vecchia, Marta Cortesi, Alice Fontana, Laura Pesant, Matthieu Maitz, Silvia Tabano, Silvia Bodega, Beatrice Miozzo, Monica Sirchia, Silvia M. Sci Rep Article Beckwith-Wiedemann syndrome (BWS) and Silver-Russell syndrome (SRS) are imprinting-related disorders associated with genetic/epigenetic alterations of the 11p15.5 region, which harbours two clusters of imprinted genes (IGs). 11p15.5 IGs are regulated by the methylation status of imprinting control regions ICR1 and ICR2. 3D chromatin structure is thought to play a pivotal role in gene expression control; however, chromatin architecture models are still poorly defined in most cases, particularly for IGs. Our study aimed at elucidating 11p15.5 3D structure, via 3C and 3D FISH analyses of cell lines derived from healthy, BWS or SRS children. We found that, in healthy cells, IGF2/H19 and CDKN1C/KCNQ1OT1 domains fold in complex chromatin conformations, that facilitate the control of IGs mediated by distant enhancers. In patient-derived cell lines, we observed a profound impairment of such a chromatin architecture. Specifically, we identified a cross-talk between IGF2/H19 and CDKN1C/KCNQ1OT1 domains, consisting in in cis, monoallelic interactions, that are present in healthy cells but lost in patient cell lines: an inter-domain association that sees ICR2 move close to IGF2 on one allele, and to H19 on the other. Moreover, an intra-domain association within the CDKN1C/KCNQ1OT1 locus seems to be crucial for maintaining the 3D organization of the region. Nature Publishing Group UK 2020-05-19 /pmc/articles/PMC7237657/ /pubmed/32427849 http://dx.doi.org/10.1038/s41598-020-65082-1 Text en © The Author(s) 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Rovina, Davide
La Vecchia, Marta
Cortesi, Alice
Fontana, Laura
Pesant, Matthieu
Maitz, Silvia
Tabano, Silvia
Bodega, Beatrice
Miozzo, Monica
Sirchia, Silvia M.
Profound alterations of the chromatin architecture at chromosome 11p15.5 in cells from Beckwith-Wiedemann and Silver-Russell syndromes patients
title Profound alterations of the chromatin architecture at chromosome 11p15.5 in cells from Beckwith-Wiedemann and Silver-Russell syndromes patients
title_full Profound alterations of the chromatin architecture at chromosome 11p15.5 in cells from Beckwith-Wiedemann and Silver-Russell syndromes patients
title_fullStr Profound alterations of the chromatin architecture at chromosome 11p15.5 in cells from Beckwith-Wiedemann and Silver-Russell syndromes patients
title_full_unstemmed Profound alterations of the chromatin architecture at chromosome 11p15.5 in cells from Beckwith-Wiedemann and Silver-Russell syndromes patients
title_short Profound alterations of the chromatin architecture at chromosome 11p15.5 in cells from Beckwith-Wiedemann and Silver-Russell syndromes patients
title_sort profound alterations of the chromatin architecture at chromosome 11p15.5 in cells from beckwith-wiedemann and silver-russell syndromes patients
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7237657/
https://www.ncbi.nlm.nih.gov/pubmed/32427849
http://dx.doi.org/10.1038/s41598-020-65082-1
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