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Satb1 integrates DNA binding site geometry and torsional stress to differentially target nucleosome-dense regions
The Satb1 genome organizer regulates multiple cellular and developmental processes. It is not yet clear how Satb1 selects different sets of targets throughout the genome. Here we have used live-cell single molecule imaging and deep sequencing to assess determinants of Satb1 binding-site selectivity....
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6642133/ https://www.ncbi.nlm.nih.gov/pubmed/31324780 http://dx.doi.org/10.1038/s41467-019-11118-8 |
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author | Ghosh, Rajarshi P. Shi, Quanming Yang, Linfeng Reddick, Michael P. Nikitina, Tatiana Zhurkin, Victor B. Fordyce, Polly Stasevich, Timothy J. Chang, Howard Y. Greenleaf, William J. Liphardt, Jan T. |
author_facet | Ghosh, Rajarshi P. Shi, Quanming Yang, Linfeng Reddick, Michael P. Nikitina, Tatiana Zhurkin, Victor B. Fordyce, Polly Stasevich, Timothy J. Chang, Howard Y. Greenleaf, William J. Liphardt, Jan T. |
author_sort | Ghosh, Rajarshi P. |
collection | PubMed |
description | The Satb1 genome organizer regulates multiple cellular and developmental processes. It is not yet clear how Satb1 selects different sets of targets throughout the genome. Here we have used live-cell single molecule imaging and deep sequencing to assess determinants of Satb1 binding-site selectivity. We have found that Satb1 preferentially targets nucleosome-dense regions and can directly bind consensus motifs within nucleosomes. Some genomic regions harbor multiple, regularly spaced Satb1 binding motifs (typical separation ~1 turn of the DNA helix) characterized by highly cooperative binding. The Satb1 homeodomain is dispensable for high affinity binding but is essential for specificity. Finally, we find that Satb1-DNA interactions are mechanosensitive. Increasing negative torsional stress in DNA enhances Satb1 binding and Satb1 stabilizes base unpairing regions against melting by molecular machines. The ability of Satb1 to control diverse biological programs may reflect its ability to combinatorially use multiple site selection criteria. |
format | Online Article Text |
id | pubmed-6642133 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-66421332019-07-22 Satb1 integrates DNA binding site geometry and torsional stress to differentially target nucleosome-dense regions Ghosh, Rajarshi P. Shi, Quanming Yang, Linfeng Reddick, Michael P. Nikitina, Tatiana Zhurkin, Victor B. Fordyce, Polly Stasevich, Timothy J. Chang, Howard Y. Greenleaf, William J. Liphardt, Jan T. Nat Commun Article The Satb1 genome organizer regulates multiple cellular and developmental processes. It is not yet clear how Satb1 selects different sets of targets throughout the genome. Here we have used live-cell single molecule imaging and deep sequencing to assess determinants of Satb1 binding-site selectivity. We have found that Satb1 preferentially targets nucleosome-dense regions and can directly bind consensus motifs within nucleosomes. Some genomic regions harbor multiple, regularly spaced Satb1 binding motifs (typical separation ~1 turn of the DNA helix) characterized by highly cooperative binding. The Satb1 homeodomain is dispensable for high affinity binding but is essential for specificity. Finally, we find that Satb1-DNA interactions are mechanosensitive. Increasing negative torsional stress in DNA enhances Satb1 binding and Satb1 stabilizes base unpairing regions against melting by molecular machines. The ability of Satb1 to control diverse biological programs may reflect its ability to combinatorially use multiple site selection criteria. Nature Publishing Group UK 2019-07-19 /pmc/articles/PMC6642133/ /pubmed/31324780 http://dx.doi.org/10.1038/s41467-019-11118-8 Text en © The Author(s) 2019 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Ghosh, Rajarshi P. Shi, Quanming Yang, Linfeng Reddick, Michael P. Nikitina, Tatiana Zhurkin, Victor B. Fordyce, Polly Stasevich, Timothy J. Chang, Howard Y. Greenleaf, William J. Liphardt, Jan T. Satb1 integrates DNA binding site geometry and torsional stress to differentially target nucleosome-dense regions |
title | Satb1 integrates DNA binding site geometry and torsional stress to differentially target nucleosome-dense regions |
title_full | Satb1 integrates DNA binding site geometry and torsional stress to differentially target nucleosome-dense regions |
title_fullStr | Satb1 integrates DNA binding site geometry and torsional stress to differentially target nucleosome-dense regions |
title_full_unstemmed | Satb1 integrates DNA binding site geometry and torsional stress to differentially target nucleosome-dense regions |
title_short | Satb1 integrates DNA binding site geometry and torsional stress to differentially target nucleosome-dense regions |
title_sort | satb1 integrates dna binding site geometry and torsional stress to differentially target nucleosome-dense regions |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6642133/ https://www.ncbi.nlm.nih.gov/pubmed/31324780 http://dx.doi.org/10.1038/s41467-019-11118-8 |
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