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The contribution of cohesin-SA1 to gene expression and chromatin architecture in two murine tissues
Cohesin, which in somatic vertebrate cells consists of SMC1, SMC3, RAD21 and either SA1 or SA2, mediates higher-order chromatin organization. To determine how cohesin contributes to the establishment of tissue-specific transcriptional programs, we compared genome-wide cohesin distribution, gene expr...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4381060/ https://www.ncbi.nlm.nih.gov/pubmed/25735743 http://dx.doi.org/10.1093/nar/gkv144 |
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author | Cuadrado, Ana Remeseiro, Silvia Graña, Osvaldo Pisano, David G. Losada, Ana |
author_facet | Cuadrado, Ana Remeseiro, Silvia Graña, Osvaldo Pisano, David G. Losada, Ana |
author_sort | Cuadrado, Ana |
collection | PubMed |
description | Cohesin, which in somatic vertebrate cells consists of SMC1, SMC3, RAD21 and either SA1 or SA2, mediates higher-order chromatin organization. To determine how cohesin contributes to the establishment of tissue-specific transcriptional programs, we compared genome-wide cohesin distribution, gene expression and chromatin architecture in cerebral cortex and pancreas from adult mice. More than one third of cohesin binding sites differ between the two tissues and these show reduced overlap with CCCTC-binding factor (CTCF) and are enriched at the regulatory regions of tissue-specific genes. Cohesin/CTCF sites at active enhancers and promoters contain, at least, cohesin-SA1. Analyses of chromatin contacts at the Protocadherin (Pcdh) and Regenerating islet-derived (Reg) gene clusters, mostly expressed in brain and pancreas, respectively, revealed remarkable differences that correlate with the presence of cohesin. We could not detect significant changes in the chromatin contacts at the Pcdh locus when comparing brains from wild-type and SA1 null embryos. In contrast, reduced dosage of SA1 altered the architecture of the Reg locus and decreased the expression of Reg genes in the pancreas of SA1 heterozygous mice. Given the role of Reg proteins in inflammation, such reduction may contribute to the increased incidence of pancreatic cancer observed in these animals. |
format | Online Article Text |
id | pubmed-4381060 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-43810602015-04-03 The contribution of cohesin-SA1 to gene expression and chromatin architecture in two murine tissues Cuadrado, Ana Remeseiro, Silvia Graña, Osvaldo Pisano, David G. Losada, Ana Nucleic Acids Res Gene regulation, Chromatin and Epigenetics Cohesin, which in somatic vertebrate cells consists of SMC1, SMC3, RAD21 and either SA1 or SA2, mediates higher-order chromatin organization. To determine how cohesin contributes to the establishment of tissue-specific transcriptional programs, we compared genome-wide cohesin distribution, gene expression and chromatin architecture in cerebral cortex and pancreas from adult mice. More than one third of cohesin binding sites differ between the two tissues and these show reduced overlap with CCCTC-binding factor (CTCF) and are enriched at the regulatory regions of tissue-specific genes. Cohesin/CTCF sites at active enhancers and promoters contain, at least, cohesin-SA1. Analyses of chromatin contacts at the Protocadherin (Pcdh) and Regenerating islet-derived (Reg) gene clusters, mostly expressed in brain and pancreas, respectively, revealed remarkable differences that correlate with the presence of cohesin. We could not detect significant changes in the chromatin contacts at the Pcdh locus when comparing brains from wild-type and SA1 null embryos. In contrast, reduced dosage of SA1 altered the architecture of the Reg locus and decreased the expression of Reg genes in the pancreas of SA1 heterozygous mice. Given the role of Reg proteins in inflammation, such reduction may contribute to the increased incidence of pancreatic cancer observed in these animals. Oxford University Press 2015-03-31 2015-03-03 /pmc/articles/PMC4381060/ /pubmed/25735743 http://dx.doi.org/10.1093/nar/gkv144 Text en © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research. http://creativecommons.org/licenses/by-nc/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com |
spellingShingle | Gene regulation, Chromatin and Epigenetics Cuadrado, Ana Remeseiro, Silvia Graña, Osvaldo Pisano, David G. Losada, Ana The contribution of cohesin-SA1 to gene expression and chromatin architecture in two murine tissues |
title | The contribution of cohesin-SA1 to gene expression and chromatin architecture in two murine tissues |
title_full | The contribution of cohesin-SA1 to gene expression and chromatin architecture in two murine tissues |
title_fullStr | The contribution of cohesin-SA1 to gene expression and chromatin architecture in two murine tissues |
title_full_unstemmed | The contribution of cohesin-SA1 to gene expression and chromatin architecture in two murine tissues |
title_short | The contribution of cohesin-SA1 to gene expression and chromatin architecture in two murine tissues |
title_sort | contribution of cohesin-sa1 to gene expression and chromatin architecture in two murine tissues |
topic | Gene regulation, Chromatin and Epigenetics |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4381060/ https://www.ncbi.nlm.nih.gov/pubmed/25735743 http://dx.doi.org/10.1093/nar/gkv144 |
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