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Satb1integrates DNA sequence,shape, motif densityand torsional stressto differentially bind targets in nucleosome-dense regions

Rajarshi P. Ghosh, Quanming Shi, Linfeng Yang, Michael P. Reddick, Tatiana Nikitina, Victor B. Zhurkin, Polly Fordyce, Timothy J. Stasevich, Howard Y. Chang, William J. Greenleaf, Jan T. Liphardt
doi: https://doi.org/10.1101/450262
Rajarshi P. Ghosh
1Bioengineering, Stanford University, Stanford, CA 94305, USA
2BioX Institute, Stanford University, Stanford, CA 94305, USA
3ChEM-H, Stanford University, Stanford, CA 94305, USA
4Cell Biology Division, Stanford Cancer Institute, Stanford, CA 94305, USA
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  • For correspondence: rajarshi@stanford.edu jan.liphardt@stanford.edu
Quanming Shi
1Bioengineering, Stanford University, Stanford, CA 94305, USA
2BioX Institute, Stanford University, Stanford, CA 94305, USA
3ChEM-H, Stanford University, Stanford, CA 94305, USA
4Cell Biology Division, Stanford Cancer Institute, Stanford, CA 94305, USA
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Linfeng Yang
1Bioengineering, Stanford University, Stanford, CA 94305, USA
2BioX Institute, Stanford University, Stanford, CA 94305, USA
3ChEM-H, Stanford University, Stanford, CA 94305, USA
4Cell Biology Division, Stanford Cancer Institute, Stanford, CA 94305, USA
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Michael P. Reddick
1Bioengineering, Stanford University, Stanford, CA 94305, USA
2BioX Institute, Stanford University, Stanford, CA 94305, USA
3ChEM-H, Stanford University, Stanford, CA 94305, USA
4Cell Biology Division, Stanford Cancer Institute, Stanford, CA 94305, USA
5Chemical Engineering, Stanford University, Stanford, CA 94305, USA
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Tatiana Nikitina
6Laboratory of Cell Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
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Victor B. Zhurkin
6Laboratory of Cell Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
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Polly Fordyce
1Bioengineering, Stanford University, Stanford, CA 94305, USA
3ChEM-H, Stanford University, Stanford, CA 94305, USA
7Department of Genetics, Stanford University, Stanford, CA 94305, USA
8Chan Zuckerberg Biohub, San Francisco, CA 94158, USA
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Timothy J. Stasevich
9Department of Biochemistry and Molecular Biology and the Institute for Genome Architecture and Function, Colorado State University, Fort Collins, CO, USA
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Howard Y. Chang
7Department of Genetics, Stanford University, Stanford, CA 94305, USA
10Center for Personal Dynamic Regulomes, Stanford University, Stanford, CA 94305, USA
11Program in Epithelial Biology, Stanford University School of Medicine, Stanford, CA 94305, USA.
12Howard Hughes Medical Institute, Stanford University, Stanford, CA, USA
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William J. Greenleaf
7Department of Genetics, Stanford University, Stanford, CA 94305, USA
13Department of Applied Physics, Stanford University, Stanford, United States
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Jan T. Liphardt
1Bioengineering, Stanford University, Stanford, CA 94305, USA
2BioX Institute, Stanford University, Stanford, CA 94305, USA
3ChEM-H, Stanford University, Stanford, CA 94305, USA
4Cell Biology Division, Stanford Cancer Institute, Stanford, CA 94305, USA
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  • For correspondence: rajarshi@stanford.edu jan.liphardt@stanford.edu
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Abstract

Satb1 is a genome organizer that regulates multiple cellular and developmental processes. It is not yet clear how Satb1 selects different sets of targets throughout the genome. We used live-cell single molecule imaging and deep sequencing to assess determinants of Satb1 binding-site selectivity. We 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, Satb1⇔DNA interactions are mechanosensitive: increasing negative torsional stress in DNA enhances Satb1 binding and Satb1 stabilizes base unpairing regions (BURs) 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.

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Posted October 26, 2018.
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Satb1integrates DNA sequence,shape, motif densityand torsional stressto differentially bind targets in nucleosome-dense regions
Rajarshi P. Ghosh, Quanming Shi, Linfeng Yang, Michael P. Reddick, Tatiana Nikitina, Victor B. Zhurkin, Polly Fordyce, Timothy J. Stasevich, Howard Y. Chang, William J. Greenleaf, Jan T. Liphardt
bioRxiv 450262; doi: https://doi.org/10.1101/450262
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Satb1integrates DNA sequence,shape, motif densityand torsional stressto differentially bind targets in nucleosome-dense regions
Rajarshi P. Ghosh, Quanming Shi, Linfeng Yang, Michael P. Reddick, Tatiana Nikitina, Victor B. Zhurkin, Polly Fordyce, Timothy J. Stasevich, Howard Y. Chang, William J. Greenleaf, Jan T. Liphardt
bioRxiv 450262; doi: https://doi.org/10.1101/450262

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