Satb1 integrates DNA binding site geometry and torsional stress to differentially target 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 and Jan T. Liphardt ()
Additional contact information
Rajarshi P. Ghosh: Stanford University
Quanming Shi: Stanford University
Linfeng Yang: Stanford University
Michael P. Reddick: Stanford University
Tatiana Nikitina: National Cancer Institute, National Institutes of Health
Victor B. Zhurkin: National Cancer Institute, National Institutes of Health
Polly Fordyce: Stanford University
Timothy J. Stasevich: Colorado State University
Howard Y. Chang: Stanford University
William J. Greenleaf: Stanford University
Jan T. Liphardt: Stanford University

Nature Communications, 2019, vol. 10, issue 1, 1-16

Abstract: Abstract 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.

Date: 2019
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DOI: 10.1038/s41467-019-11118-8

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