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Dissecting OCT4 defines the role of nucleosome binding in pluripotency
Pioneer transcription factors (TFs) such as OCT4 can target silent genes embedded in nucleosome-dense regions. How nucleosome interaction enables TFs to target chromatin and determine cell identity remains elusive. Here, we systematically dissect OCT4 to show that nucleosome binding is encoded withi...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7611526/ https://www.ncbi.nlm.nih.gov/pubmed/34354236 http://dx.doi.org/10.1038/s41556-021-00727-5 |
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author | Roberts, Gareth A. Ozkan, Burak Gachulincová, Ivana O’Dwyer, Michael R. Hall-Ponsele, Elisa Saxena, Manoj Robinson, Philip J. Soufi, Abdenour |
author_facet | Roberts, Gareth A. Ozkan, Burak Gachulincová, Ivana O’Dwyer, Michael R. Hall-Ponsele, Elisa Saxena, Manoj Robinson, Philip J. Soufi, Abdenour |
author_sort | Roberts, Gareth A. |
collection | PubMed |
description | Pioneer transcription factors (TFs) such as OCT4 can target silent genes embedded in nucleosome-dense regions. How nucleosome interaction enables TFs to target chromatin and determine cell identity remains elusive. Here, we systematically dissect OCT4 to show that nucleosome binding is encoded within the DNA-binding domain and yet can be uncoupled from free DNA binding. Furthermore, accelerating the binding kinetics of OCT4 to DNA enhances nucleosome binding. In cells, uncoupling nucleosome binding diminishes the ability of OCT4 to individually access closed chromatin, while more dynamic nucleosome binding results in expansive genome scanning within closed chromatin. However, both uncoupling and enhancing nucleosome binding are detrimental to inducing pluripotency from differentiated cells. Remarkably, stable interactions between OCT4 and nucleosomes are continuously required for maintaining the accessibility of pluripotency enhancers in stem cells. Our findings reveal how the affinity and residence time of OCT4-nucleosome complexes modulate chromatin accessibility during cell fate changes and maintenance. |
format | Online Article Text |
id | pubmed-7611526 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
record_format | MEDLINE/PubMed |
spelling | pubmed-76115262022-02-05 Dissecting OCT4 defines the role of nucleosome binding in pluripotency Roberts, Gareth A. Ozkan, Burak Gachulincová, Ivana O’Dwyer, Michael R. Hall-Ponsele, Elisa Saxena, Manoj Robinson, Philip J. Soufi, Abdenour Nat Cell Biol Article Pioneer transcription factors (TFs) such as OCT4 can target silent genes embedded in nucleosome-dense regions. How nucleosome interaction enables TFs to target chromatin and determine cell identity remains elusive. Here, we systematically dissect OCT4 to show that nucleosome binding is encoded within the DNA-binding domain and yet can be uncoupled from free DNA binding. Furthermore, accelerating the binding kinetics of OCT4 to DNA enhances nucleosome binding. In cells, uncoupling nucleosome binding diminishes the ability of OCT4 to individually access closed chromatin, while more dynamic nucleosome binding results in expansive genome scanning within closed chromatin. However, both uncoupling and enhancing nucleosome binding are detrimental to inducing pluripotency from differentiated cells. Remarkably, stable interactions between OCT4 and nucleosomes are continuously required for maintaining the accessibility of pluripotency enhancers in stem cells. Our findings reveal how the affinity and residence time of OCT4-nucleosome complexes modulate chromatin accessibility during cell fate changes and maintenance. 2021-08-01 2021-08-05 /pmc/articles/PMC7611526/ /pubmed/34354236 http://dx.doi.org/10.1038/s41556-021-00727-5 Text en https://www.springernature.com/gp/open-research/policies/accepted-manuscript-termsUsers may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: https://www.springernature.com/gp/open-research/policies/accepted-manuscript-terms |
spellingShingle | Article Roberts, Gareth A. Ozkan, Burak Gachulincová, Ivana O’Dwyer, Michael R. Hall-Ponsele, Elisa Saxena, Manoj Robinson, Philip J. Soufi, Abdenour Dissecting OCT4 defines the role of nucleosome binding in pluripotency |
title | Dissecting OCT4 defines the role of nucleosome binding in pluripotency |
title_full | Dissecting OCT4 defines the role of nucleosome binding in pluripotency |
title_fullStr | Dissecting OCT4 defines the role of nucleosome binding in pluripotency |
title_full_unstemmed | Dissecting OCT4 defines the role of nucleosome binding in pluripotency |
title_short | Dissecting OCT4 defines the role of nucleosome binding in pluripotency |
title_sort | dissecting oct4 defines the role of nucleosome binding in pluripotency |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7611526/ https://www.ncbi.nlm.nih.gov/pubmed/34354236 http://dx.doi.org/10.1038/s41556-021-00727-5 |
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