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Functional and topological characteristics of mammalian regulatory domains

Long-range regulatory interactions play an important role in shaping gene-expression programs. However, the genomic features that organize these activities are still poorly characterized. We conducted a large operational analysis to chart the distribution of gene regulatory activities along the mous...

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Autores principales: Symmons, Orsolya, Uslu, Veli Vural, Tsujimura, Taro, Ruf, Sandra, Nassari, Sonya, Schwarzer, Wibke, Ettwiller, Laurence, Spitz, François
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cold Spring Harbor Laboratory Press 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3941104/
https://www.ncbi.nlm.nih.gov/pubmed/24398455
http://dx.doi.org/10.1101/gr.163519.113
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author Symmons, Orsolya
Uslu, Veli Vural
Tsujimura, Taro
Ruf, Sandra
Nassari, Sonya
Schwarzer, Wibke
Ettwiller, Laurence
Spitz, François
author_facet Symmons, Orsolya
Uslu, Veli Vural
Tsujimura, Taro
Ruf, Sandra
Nassari, Sonya
Schwarzer, Wibke
Ettwiller, Laurence
Spitz, François
author_sort Symmons, Orsolya
collection PubMed
description Long-range regulatory interactions play an important role in shaping gene-expression programs. However, the genomic features that organize these activities are still poorly characterized. We conducted a large operational analysis to chart the distribution of gene regulatory activities along the mouse genome, using hundreds of insertions of a regulatory sensor. We found that enhancers distribute their activities along broad regions and not in a gene-centric manner, defining large regulatory domains. Remarkably, these domains correlate strongly with the recently described TADs, which partition the genome into distinct self-interacting blocks. Different features, including specific repeats and CTCF-binding sites, correlate with the transition zones separating regulatory domains, and may help to further organize promiscuously distributed regulatory influences within large domains. These findings support a model of genomic organization where TADs confine regulatory activities to specific but large regulatory domains, contributing to the establishment of specific gene expression profiles.
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spelling pubmed-39411042014-09-01 Functional and topological characteristics of mammalian regulatory domains Symmons, Orsolya Uslu, Veli Vural Tsujimura, Taro Ruf, Sandra Nassari, Sonya Schwarzer, Wibke Ettwiller, Laurence Spitz, François Genome Res Research Long-range regulatory interactions play an important role in shaping gene-expression programs. However, the genomic features that organize these activities are still poorly characterized. We conducted a large operational analysis to chart the distribution of gene regulatory activities along the mouse genome, using hundreds of insertions of a regulatory sensor. We found that enhancers distribute their activities along broad regions and not in a gene-centric manner, defining large regulatory domains. Remarkably, these domains correlate strongly with the recently described TADs, which partition the genome into distinct self-interacting blocks. Different features, including specific repeats and CTCF-binding sites, correlate with the transition zones separating regulatory domains, and may help to further organize promiscuously distributed regulatory influences within large domains. These findings support a model of genomic organization where TADs confine regulatory activities to specific but large regulatory domains, contributing to the establishment of specific gene expression profiles. Cold Spring Harbor Laboratory Press 2014-03 /pmc/articles/PMC3941104/ /pubmed/24398455 http://dx.doi.org/10.1101/gr.163519.113 Text en © 2014 Symmons et al.; Published by Cold Spring Harbor Laboratory Press http://creativecommons.org/licenses/by-nc/3.0/ This article is distributed exclusively by Cold Spring Harbor Laboratory Press for the first six months after the full-issue publication date (see http://genome.cshlp.org/site/misc/terms.xhtml). After six months, it is available under a Creative Commons License (Attribution-NonCommercial 3.0 Unported), as described at http://creativecommons.org/licenses/by-nc/3.0/.
spellingShingle Research
Symmons, Orsolya
Uslu, Veli Vural
Tsujimura, Taro
Ruf, Sandra
Nassari, Sonya
Schwarzer, Wibke
Ettwiller, Laurence
Spitz, François
Functional and topological characteristics of mammalian regulatory domains
title Functional and topological characteristics of mammalian regulatory domains
title_full Functional and topological characteristics of mammalian regulatory domains
title_fullStr Functional and topological characteristics of mammalian regulatory domains
title_full_unstemmed Functional and topological characteristics of mammalian regulatory domains
title_short Functional and topological characteristics of mammalian regulatory domains
title_sort functional and topological characteristics of mammalian regulatory domains
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3941104/
https://www.ncbi.nlm.nih.gov/pubmed/24398455
http://dx.doi.org/10.1101/gr.163519.113
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