Live-cell imaging reveals enhancer-dependent Sox2 transcription in the absence of enhancer proximity

Enhancers are important regulatory elements that can control gene activity across vast genetic distances. However, the underlying nature of this regulation remains obscured because it has been difficult to observe in living cells. Here, we visualize the spatial organization and transcriptional outpu...

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Autores principales: Alexander, Jeffrey M, Guan, Juan, Li, Bingkun, Maliskova, Lenka, Song, Michael, Shen, Yin, Huang, Bo, Lomvardas, Stavros, Weiner, Orion D
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6534382/
https://www.ncbi.nlm.nih.gov/pubmed/31124784
http://dx.doi.org/10.7554/eLife.41769
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author Alexander, Jeffrey M
Guan, Juan
Li, Bingkun
Maliskova, Lenka
Song, Michael
Shen, Yin
Huang, Bo
Lomvardas, Stavros
Weiner, Orion D
author_facet Alexander, Jeffrey M
Guan, Juan
Li, Bingkun
Maliskova, Lenka
Song, Michael
Shen, Yin
Huang, Bo
Lomvardas, Stavros
Weiner, Orion D
author_sort Alexander, Jeffrey M
collection PubMed
description Enhancers are important regulatory elements that can control gene activity across vast genetic distances. However, the underlying nature of this regulation remains obscured because it has been difficult to observe in living cells. Here, we visualize the spatial organization and transcriptional output of the key pluripotency regulator Sox2 and its essential enhancer Sox2 Control Region (SCR) in living embryonic stem cells (ESCs). We find that Sox2 and SCR show no evidence of enhanced spatial proximity and that spatial dynamics of this pair is limited over tens of minutes. Sox2 transcription occurs in short, intermittent bursts in ESCs and, intriguingly, we find this activity demonstrates no association with enhancer proximity, suggesting that direct enhancer-promoter contacts do not drive contemporaneous Sox2 transcription. Our study establishes a framework for interrogation of enhancer function in living cells and supports an unexpected mechanism for enhancer control of Sox2 expression that uncouples transcription from enhancer proximity.
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spelling pubmed-65343822019-05-28 Live-cell imaging reveals enhancer-dependent Sox2 transcription in the absence of enhancer proximity Alexander, Jeffrey M Guan, Juan Li, Bingkun Maliskova, Lenka Song, Michael Shen, Yin Huang, Bo Lomvardas, Stavros Weiner, Orion D eLife Chromosomes and Gene Expression Enhancers are important regulatory elements that can control gene activity across vast genetic distances. However, the underlying nature of this regulation remains obscured because it has been difficult to observe in living cells. Here, we visualize the spatial organization and transcriptional output of the key pluripotency regulator Sox2 and its essential enhancer Sox2 Control Region (SCR) in living embryonic stem cells (ESCs). We find that Sox2 and SCR show no evidence of enhanced spatial proximity and that spatial dynamics of this pair is limited over tens of minutes. Sox2 transcription occurs in short, intermittent bursts in ESCs and, intriguingly, we find this activity demonstrates no association with enhancer proximity, suggesting that direct enhancer-promoter contacts do not drive contemporaneous Sox2 transcription. Our study establishes a framework for interrogation of enhancer function in living cells and supports an unexpected mechanism for enhancer control of Sox2 expression that uncouples transcription from enhancer proximity. eLife Sciences Publications, Ltd 2019-05-24 /pmc/articles/PMC6534382/ /pubmed/31124784 http://dx.doi.org/10.7554/eLife.41769 Text en © 2019, Alexander et al http://creativecommons.org/licenses/by/4.0/ http://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Chromosomes and Gene Expression
Alexander, Jeffrey M
Guan, Juan
Li, Bingkun
Maliskova, Lenka
Song, Michael
Shen, Yin
Huang, Bo
Lomvardas, Stavros
Weiner, Orion D
Live-cell imaging reveals enhancer-dependent Sox2 transcription in the absence of enhancer proximity
title Live-cell imaging reveals enhancer-dependent Sox2 transcription in the absence of enhancer proximity
title_full Live-cell imaging reveals enhancer-dependent Sox2 transcription in the absence of enhancer proximity
title_fullStr Live-cell imaging reveals enhancer-dependent Sox2 transcription in the absence of enhancer proximity
title_full_unstemmed Live-cell imaging reveals enhancer-dependent Sox2 transcription in the absence of enhancer proximity
title_short Live-cell imaging reveals enhancer-dependent Sox2 transcription in the absence of enhancer proximity
title_sort live-cell imaging reveals enhancer-dependent sox2 transcription in the absence of enhancer proximity
topic Chromosomes and Gene Expression
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6534382/
https://www.ncbi.nlm.nih.gov/pubmed/31124784
http://dx.doi.org/10.7554/eLife.41769
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