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A dynamic interplay of enhancer elements regulates Klf4 expression in naïve pluripotency

Transcription factor (TF)-directed enhanceosome assembly constitutes a fundamental regulatory mechanism driving spatiotemporal gene expression programs during animal development. Despite decades of study, we know little about the dynamics or order of events animating TF assembly at cis-regulatory el...

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Autores principales: Xie, Liangqi, Torigoe, Sharon E., Xiao, Jifang, Mai, Daniel H., Li, Li, Davis, Fred P., Dong, Peng, Marie-Nelly, Herve, Grimm, Jonathan, Lavis, Luke, Darzacq, Xavier, Cattoglio, Claudia, Liu, Zhe, Tjian, Robert
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cold Spring Harbor Laboratory Press 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5666677/
https://www.ncbi.nlm.nih.gov/pubmed/28982762
http://dx.doi.org/10.1101/gad.303321.117
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author Xie, Liangqi
Torigoe, Sharon E.
Xiao, Jifang
Mai, Daniel H.
Li, Li
Davis, Fred P.
Dong, Peng
Marie-Nelly, Herve
Grimm, Jonathan
Lavis, Luke
Darzacq, Xavier
Cattoglio, Claudia
Liu, Zhe
Tjian, Robert
author_facet Xie, Liangqi
Torigoe, Sharon E.
Xiao, Jifang
Mai, Daniel H.
Li, Li
Davis, Fred P.
Dong, Peng
Marie-Nelly, Herve
Grimm, Jonathan
Lavis, Luke
Darzacq, Xavier
Cattoglio, Claudia
Liu, Zhe
Tjian, Robert
author_sort Xie, Liangqi
collection PubMed
description Transcription factor (TF)-directed enhanceosome assembly constitutes a fundamental regulatory mechanism driving spatiotemporal gene expression programs during animal development. Despite decades of study, we know little about the dynamics or order of events animating TF assembly at cis-regulatory elements in living cells and the long-range molecular “dialog” between enhancers and promoters. Here, combining genetic, genomic, and imaging approaches, we characterize a complex long-range enhancer cluster governing Krüppel-like factor 4 (Klf4) expression in naïve pluripotency. Genome editing by CRISPR/Cas9 revealed that OCT4 and SOX2 safeguard an accessible chromatin neighborhood to assist the binding of other TFs/cofactors to the enhancer. Single-molecule live-cell imaging uncovered that two naïve pluripotency TFs, STAT3 and ESRRB, interrogate chromatin in a highly dynamic manner, in which SOX2 promotes ESRRB target search and chromatin-binding dynamics through a direct protein-tethering mechanism. Together, our results support a highly dynamic yet intrinsically ordered enhanceosome assembly to maintain the finely balanced transcription program underlying naïve pluripotency.
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spelling pubmed-56666772018-03-01 A dynamic interplay of enhancer elements regulates Klf4 expression in naïve pluripotency Xie, Liangqi Torigoe, Sharon E. Xiao, Jifang Mai, Daniel H. Li, Li Davis, Fred P. Dong, Peng Marie-Nelly, Herve Grimm, Jonathan Lavis, Luke Darzacq, Xavier Cattoglio, Claudia Liu, Zhe Tjian, Robert Genes Dev Research Paper Transcription factor (TF)-directed enhanceosome assembly constitutes a fundamental regulatory mechanism driving spatiotemporal gene expression programs during animal development. Despite decades of study, we know little about the dynamics or order of events animating TF assembly at cis-regulatory elements in living cells and the long-range molecular “dialog” between enhancers and promoters. Here, combining genetic, genomic, and imaging approaches, we characterize a complex long-range enhancer cluster governing Krüppel-like factor 4 (Klf4) expression in naïve pluripotency. Genome editing by CRISPR/Cas9 revealed that OCT4 and SOX2 safeguard an accessible chromatin neighborhood to assist the binding of other TFs/cofactors to the enhancer. Single-molecule live-cell imaging uncovered that two naïve pluripotency TFs, STAT3 and ESRRB, interrogate chromatin in a highly dynamic manner, in which SOX2 promotes ESRRB target search and chromatin-binding dynamics through a direct protein-tethering mechanism. Together, our results support a highly dynamic yet intrinsically ordered enhanceosome assembly to maintain the finely balanced transcription program underlying naïve pluripotency. Cold Spring Harbor Laboratory Press 2017-09-01 /pmc/articles/PMC5666677/ /pubmed/28982762 http://dx.doi.org/10.1101/gad.303321.117 Text en © 2017 Xie et al.; Published by Cold Spring Harbor Laboratory Press http://creativecommons.org/licenses/by-nc/4.0/ This article is distributed exclusively by Cold Spring Harbor Laboratory Press for the first six months after the full-issue publication date (see http://genesdev.cshlp.org/site/misc/terms.xhtml). After six months, it is available under a Creative Commons License (Attribution-NonCommercial 4.0 International), as described at http://creativecommons.org/licenses/by-nc/4.0/.
spellingShingle Research Paper
Xie, Liangqi
Torigoe, Sharon E.
Xiao, Jifang
Mai, Daniel H.
Li, Li
Davis, Fred P.
Dong, Peng
Marie-Nelly, Herve
Grimm, Jonathan
Lavis, Luke
Darzacq, Xavier
Cattoglio, Claudia
Liu, Zhe
Tjian, Robert
A dynamic interplay of enhancer elements regulates Klf4 expression in naïve pluripotency
title A dynamic interplay of enhancer elements regulates Klf4 expression in naïve pluripotency
title_full A dynamic interplay of enhancer elements regulates Klf4 expression in naïve pluripotency
title_fullStr A dynamic interplay of enhancer elements regulates Klf4 expression in naïve pluripotency
title_full_unstemmed A dynamic interplay of enhancer elements regulates Klf4 expression in naïve pluripotency
title_short A dynamic interplay of enhancer elements regulates Klf4 expression in naïve pluripotency
title_sort dynamic interplay of enhancer elements regulates klf4 expression in naïve pluripotency
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5666677/
https://www.ncbi.nlm.nih.gov/pubmed/28982762
http://dx.doi.org/10.1101/gad.303321.117
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