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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...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Cold Spring Harbor Laboratory Press
2017
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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. |
format | Online Article Text |
id | pubmed-5666677 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Cold Spring Harbor Laboratory Press |
record_format | MEDLINE/PubMed |
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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