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Series GSE123292 Query DataSets for GSE123292
Status Public on May 28, 2019
Title Satb1 integrates DNA sequence, shape, motif density and torsional stress to selectively bind a subset of putative targets in nucleosome-dense regions of the genome
Organisms Homo sapiens; Mus musculus
Experiment type Genome binding/occupancy profiling by high throughput sequencing
Summary Satb1 (Special AT-rich sequence binding protein 1) coordinates chromatin architecture and regulates a diverse set of cellular and developmental processes. It is not yet clear how Satb1 selects it targets throughout the genome and which cellular parameters modulate its binding landscape. We have used single molecule live cell imaging and deep sequencing to quantify the arrangement of SatB1 molecules in the living nucleus and relate those spatial patterns to specific genomic features. We found that Satb1 preferentially binds to nucleosome dense regions and can access consensus motifs embedded in nucleosomes, features that epitomize 'pioneer' factors. Super-resolution live cell microscopy paired with deep sequencing showed that Satb1 binds iteratively to a set of closely clustered binding sites in the nucleus, and that binding is highly cooperative in regions with high motif density. Further, we observed that Satb1 uses DNA shape information from motif-flanking regions to narrow its binding spectrum. Satb1/DNA interactions were mechanosensitive. Increasing negative torsional stress enhanced binding and Satb1 stabilized base unpairing regions (BURs) against melting by molecular machines such as topoisomerases. Indeed, the ability of a small number of 'master' regulators to control diverse biological programs suggests that these regulators must use a multiparameter, combinatorial logic to select the cell-type and temporally appropriate chromatin state
Overall design Analysis of the interaction of Satb1 and Chromatin by coupling various genomics tools and high resolution imaging
Contributor(s) Liphardt J, Shi Q
Citation(s) 31324780
Submission date Dec 03, 2018
Last update date Jul 30, 2019
Contact name Jan Liphardt
Phone 6504983560
Organization name Stanford university
Department Bioengineering
Street address 443 Via Ortega, Shriram Center 020
City Stanford
State/province California
ZIP/Postal code 94305
Country USA
Platforms (3)
GPL9052 Illumina Genome Analyzer (Homo sapiens)
GPL18573 Illumina NextSeq 500 (Homo sapiens)
GPL19057 Illumina NextSeq 500 (Mus musculus)
Samples (20)
GSM3499388 MCF10A_satb1_CHIP_seq
GSM3499389 MCF10A_deltaHD_CHIP_seq
GSM3499390 MCF10A_NC1_CHIP_seq
BioProject PRJNA508195
SRA SRP172100

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Supplementary file Size Download File type/resource
GSE123292_RAW.tar 3.7 Gb (http)(custom) TAR (of BROADPEAK, BW, NARROWPEAK)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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