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Novel long-range regulatory mechanisms controlling PKD2 gene expression
BACKGROUND: Cis-regulatory elements control gene expression over large distances through the formation of chromatin loops, which allow contact between enhancers and gene promoters. Alterations in cis-acting regulatory systems could be linked to human genetic diseases. Here, we analyse the spatial or...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6038307/ https://www.ncbi.nlm.nih.gov/pubmed/29986647 http://dx.doi.org/10.1186/s12864-018-4892-6 |
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author | Moisan, Stéphanie Levon, Stéphanie Cornec-Le Gall, Emilie Le Meur, Yannick Audrézet, Marie-Pierre Dostie, Josée Férec, Claude |
author_facet | Moisan, Stéphanie Levon, Stéphanie Cornec-Le Gall, Emilie Le Meur, Yannick Audrézet, Marie-Pierre Dostie, Josée Férec, Claude |
author_sort | Moisan, Stéphanie |
collection | PubMed |
description | BACKGROUND: Cis-regulatory elements control gene expression over large distances through the formation of chromatin loops, which allow contact between enhancers and gene promoters. Alterations in cis-acting regulatory systems could be linked to human genetic diseases. Here, we analyse the spatial organization of a large region spanning the polycystic kidney disease 2 (PKD2) gene, one of the genes responsible of autosomal dominant polycystic kidney disease (ADPKD). RESULTS: By using chromosome conformation capture carbon copy (5C) technology in primary human renal cyst epithelial cells, we identify novel contacts of the PKD2 promoter with chromatin regions, which display characteristics of regulatory elements. In parallel, by using functional analysis with a reporter assay, we demonstrate that three DNAse I hypersensitive sites regions are involved in the regulation of PKD2 gene expression. CONCLUSIONS: Finally, through alignment of CCCTC-binding factor (CTCF) sites, we suggest that these novel enhancer elements are brought to the PKD2 promoter by chromatin looping via the recruitment of CTCF. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12864-018-4892-6) contains supplementary material, which is available to authorized users. |
format | Online Article Text |
id | pubmed-6038307 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-60383072018-07-12 Novel long-range regulatory mechanisms controlling PKD2 gene expression Moisan, Stéphanie Levon, Stéphanie Cornec-Le Gall, Emilie Le Meur, Yannick Audrézet, Marie-Pierre Dostie, Josée Férec, Claude BMC Genomics Research Article BACKGROUND: Cis-regulatory elements control gene expression over large distances through the formation of chromatin loops, which allow contact between enhancers and gene promoters. Alterations in cis-acting regulatory systems could be linked to human genetic diseases. Here, we analyse the spatial organization of a large region spanning the polycystic kidney disease 2 (PKD2) gene, one of the genes responsible of autosomal dominant polycystic kidney disease (ADPKD). RESULTS: By using chromosome conformation capture carbon copy (5C) technology in primary human renal cyst epithelial cells, we identify novel contacts of the PKD2 promoter with chromatin regions, which display characteristics of regulatory elements. In parallel, by using functional analysis with a reporter assay, we demonstrate that three DNAse I hypersensitive sites regions are involved in the regulation of PKD2 gene expression. CONCLUSIONS: Finally, through alignment of CCCTC-binding factor (CTCF) sites, we suggest that these novel enhancer elements are brought to the PKD2 promoter by chromatin looping via the recruitment of CTCF. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12864-018-4892-6) contains supplementary material, which is available to authorized users. BioMed Central 2018-07-03 /pmc/articles/PMC6038307/ /pubmed/29986647 http://dx.doi.org/10.1186/s12864-018-4892-6 Text en © The Author(s). 2018 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided 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 Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Research Article Moisan, Stéphanie Levon, Stéphanie Cornec-Le Gall, Emilie Le Meur, Yannick Audrézet, Marie-Pierre Dostie, Josée Férec, Claude Novel long-range regulatory mechanisms controlling PKD2 gene expression |
title | Novel long-range regulatory mechanisms controlling PKD2 gene expression |
title_full | Novel long-range regulatory mechanisms controlling PKD2 gene expression |
title_fullStr | Novel long-range regulatory mechanisms controlling PKD2 gene expression |
title_full_unstemmed | Novel long-range regulatory mechanisms controlling PKD2 gene expression |
title_short | Novel long-range regulatory mechanisms controlling PKD2 gene expression |
title_sort | novel long-range regulatory mechanisms controlling pkd2 gene expression |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6038307/ https://www.ncbi.nlm.nih.gov/pubmed/29986647 http://dx.doi.org/10.1186/s12864-018-4892-6 |
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