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.
Highlights
The Satb[1] genome organizer regulates multiple cellular and developmental processes
transcription factors (TFs) binding is further modulated by chromatin accessibility and nucleosome occupancy[10,11] which in turn are affected by DNA torsional stress and deformability[12,13,14]
The diffusion coefficients obtained from the average of all fits showed that Satb[1] is highly dynamic in EC (5.1 ± 1.8 μm[2] s−1) and to a lesser extent at the EC/HC boundary (1.7 ± 1.1 μm[2] s−1)
Summary
The Satb[1] genome organizer regulates multiple cellular and developmental processes. It is not yet clear how Satb[1] selects different sets of targets throughout the genome. Some genomic regions harbor multiple, regularly spaced Satb[1] binding motifs (typical separation ~1 turn of the DNA helix) characterized by highly cooperative binding. At the core of cellular information processing is the ability of transcription factors (TFs) to bind subsets of genomic targets selectively. Domains (DBD) can combinatorially engage multiple distinct core DNA consensus motifs[1,2]. Transcription factors have been shown to streamline their binding choices based on the shape of regions flanking the core motif[7]. Satb[1] is a dimeric/tetrameric[16] transcription factor with multiple DNA binding domains, namely CUT1, CUT2 and a C-
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
