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Enhancer networks revealed by correlated DNAse hypersensitivity states of enhancers

Mammalian gene expression is often regulated by distal enhancers. However, little is known about higher order functional organization of enhancers. Using ∼100 K P300-bound regions as candidate enhancers, we investigated their correlated activity across 72 cell types based on DNAse hypersensitivity....

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Autores principales: Malin, Justin, Aniba, Mohamed Radhouane, Hannenhalli, Sridhar
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3737527/
https://www.ncbi.nlm.nih.gov/pubmed/23700312
http://dx.doi.org/10.1093/nar/gkt374
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author Malin, Justin
Aniba, Mohamed Radhouane
Hannenhalli, Sridhar
author_facet Malin, Justin
Aniba, Mohamed Radhouane
Hannenhalli, Sridhar
author_sort Malin, Justin
collection PubMed
description Mammalian gene expression is often regulated by distal enhancers. However, little is known about higher order functional organization of enhancers. Using ∼100 K P300-bound regions as candidate enhancers, we investigated their correlated activity across 72 cell types based on DNAse hypersensitivity. We found widespread correlated activity between enhancers, which decreases with increasing inter-enhancer genomic distance. We found that correlated enhancers tend to share common transcription factor (TF) binding motifs, and several chromatin modification enzymes preferentially interact with these TFs. Presence of shared motifs in enhancer pairs can predict correlated activity with 73% accuracy. Also, genes near correlated enhancers exhibit correlated expression and share common function. Correlated enhancers tend to be spatially proximal. Interestingly, weak enhancers tend to correlate with significantly greater numbers of other enhancers relative to strong enhancers. Furthermore, strong/weak enhancers preferentially correlate with strong/weak enhancers, respectively. We constructed enhancer networks based on shared motif and correlated activity and show significant functional enrichment in their putative target gene clusters. Overall, our analyses show extensive correlated activity among enhancers and reveal clusters of enhancers whose activities are coordinately regulated by multiple potential mechanisms involving shared TF binding, chromatin modifying enzymes and 3D chromatin structure, which ultimately co-regulate functionally linked genes.
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spelling pubmed-37375272013-08-08 Enhancer networks revealed by correlated DNAse hypersensitivity states of enhancers Malin, Justin Aniba, Mohamed Radhouane Hannenhalli, Sridhar Nucleic Acids Res Gene Regulation, Chromatin and Epigenetics Mammalian gene expression is often regulated by distal enhancers. However, little is known about higher order functional organization of enhancers. Using ∼100 K P300-bound regions as candidate enhancers, we investigated their correlated activity across 72 cell types based on DNAse hypersensitivity. We found widespread correlated activity between enhancers, which decreases with increasing inter-enhancer genomic distance. We found that correlated enhancers tend to share common transcription factor (TF) binding motifs, and several chromatin modification enzymes preferentially interact with these TFs. Presence of shared motifs in enhancer pairs can predict correlated activity with 73% accuracy. Also, genes near correlated enhancers exhibit correlated expression and share common function. Correlated enhancers tend to be spatially proximal. Interestingly, weak enhancers tend to correlate with significantly greater numbers of other enhancers relative to strong enhancers. Furthermore, strong/weak enhancers preferentially correlate with strong/weak enhancers, respectively. We constructed enhancer networks based on shared motif and correlated activity and show significant functional enrichment in their putative target gene clusters. Overall, our analyses show extensive correlated activity among enhancers and reveal clusters of enhancers whose activities are coordinately regulated by multiple potential mechanisms involving shared TF binding, chromatin modifying enzymes and 3D chromatin structure, which ultimately co-regulate functionally linked genes. Oxford University Press 2013-08 2013-05-21 /pmc/articles/PMC3737527/ /pubmed/23700312 http://dx.doi.org/10.1093/nar/gkt374 Text en © The Author(s) 2013. Published by Oxford University Press. http://creativecommons.org/licenses/by/3.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Gene Regulation, Chromatin and Epigenetics
Malin, Justin
Aniba, Mohamed Radhouane
Hannenhalli, Sridhar
Enhancer networks revealed by correlated DNAse hypersensitivity states of enhancers
title Enhancer networks revealed by correlated DNAse hypersensitivity states of enhancers
title_full Enhancer networks revealed by correlated DNAse hypersensitivity states of enhancers
title_fullStr Enhancer networks revealed by correlated DNAse hypersensitivity states of enhancers
title_full_unstemmed Enhancer networks revealed by correlated DNAse hypersensitivity states of enhancers
title_short Enhancer networks revealed by correlated DNAse hypersensitivity states of enhancers
title_sort enhancer networks revealed by correlated dnase hypersensitivity states of enhancers
topic Gene Regulation, Chromatin and Epigenetics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3737527/
https://www.ncbi.nlm.nih.gov/pubmed/23700312
http://dx.doi.org/10.1093/nar/gkt374
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