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
Rajarshi P. Ghosh
Bioengineering, Stanford University, Stanford, CA 94305, USABioX Institute, Stanford University, Stanford, CA 94305, USAChEM-H, Stanford University, Stanford, CA 94305, USACell Biology Division, Stanford Cancer Institute, Stanford, CA 94305, USA
For correspondence: rajarshi@stanford.edu jan.liphardt@stanford.edu
Quanming Shi
Linfeng Yang
Michael P. Reddick
Bioengineering, Stanford University, Stanford, CA 94305, USABioX Institute, Stanford University, Stanford, CA 94305, USAChEM-H, Stanford University, Stanford, CA 94305, USACell Biology Division, Stanford Cancer Institute, Stanford, CA 94305, USAChemical Engineering, Stanford University, Stanford, CA 94305, USA
Tatiana Nikitina
Laboratory of Cell Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
Victor B. Zhurkin
Polly Fordyce
Bioengineering, Stanford University, Stanford, CA 94305, USAChEM-H, Stanford University, Stanford, CA 94305, USADepartment of Genetics, Stanford University, Stanford, CA 94305, USAChan Zuckerberg Biohub, San Francisco, CA 94158, USA
Timothy J. Stasevich
Department of Biochemistry and Molecular Biology and the Institute for Genome Architecture and Function, Colorado State University, Fort Collins, CO, USA
Howard Y. Chang
Department of Genetics, Stanford University, Stanford, CA 94305, USACenter for Personal Dynamic Regulomes, Stanford University, Stanford, CA 94305, USAProgram in Epithelial Biology, Stanford University School of Medicine, Stanford, CA 94305, USA.Howard Hughes Medical Institute, Stanford University, Stanford, CA, USA
William J. Greenleaf
Department of Genetics, Stanford University, Stanford, CA 94305, USADepartment of Applied Physics, Stanford University, Stanford, United States
Jan T. Liphardt
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.
Posted October 26, 2018.
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