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Series GSE137193 Query DataSets for GSE137193
Status Public on Nov 21, 2020
Title ChIP-nexus data for Oct4, Sox2, Nanog and Klf4 in mouse embryonic stem cells
Organism Mus musculus
Experiment type Genome binding/occupancy profiling by high throughput sequencing
Summary The goal of this study was discover the transcription binding synthax for the key differentiation TFs in mouse embryonic stem cells.
Genes are regulated through enhancer sequences, in which transcription factor binding motifs and their specific arrangements (syntax) form a cis-regulatory code. To understand the relationship between motif syntax and transcription factor binding, we train a deep learning model that uses DNA sequence to predict base-resolution binding profiles of four pluripotency transcription factors Oct4, Sox2, Nanog, and Klf4. We interpret the model to accurately map hundreds of thousands of motifs in the genome, learn novel motif representations and identify rules by which motifs and syntax influence transcription factor binding. We find that instances of strict motif spacing are largely due to retrotransposons, but that soft motif syntax influences motif interactions at protein and nucleosome range. Most strikingly, Nanog binding is driven by motifs with a strong preference for ~10.5 bp spacings corresponding to helical periodicity. Interpreting deep learning models applied to high-resolution binding data is a powerful and versatile approach to uncover the motifs and syntax of cis-regulatory sequences.
Overall design ChIP-nexus and ChIP-seq measurements in WT ESCs R1 cell line for 4 TFs. Additionally, ChIP-nexus of Nanog and Sox2 was performed on CRISPR perturbations of Sox2 (chr10: 85,539,634-85,539,643 (mm10) mutated from CCTTTGTTCC (wildtype) to CCTAGGTTCC (mutant) and Nanog (chr10: 85,539,756-85,539,765 (mm10) mutated from CTGATGGCT (wildtype) to CGGCTGGCT).
Contributor(s) Zeitlinger J, Avsec Z, Weilert M
Citation(s) 33603233
Submission date Sep 10, 2019
Last update date Feb 28, 2021
Contact name Julia Zeitlinger
Organization name Stowers Institute for Medical Research
Lab Zeitlinger Lab
Street address 1000 E 50th Street
City Kansas City
State/province MO
ZIP/Postal code 64110
Country USA
Platforms (3)
GPL13112 Illumina HiSeq 2000 (Mus musculus)
GPL19057 Illumina NextSeq 500 (Mus musculus)
GPL24247 Illumina NovaSeq 6000 (Mus musculus)
Samples (18)
GSM4072776 Oct4-ChIP-nexus
GSM4072777 Sox2-ChIP-nexus
GSM4072778 Nanog-ChIP-nexus
BioProject PRJNA564790
SRA SRP221245

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Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE137193_RAW.tar 12.2 Gb (http)(custom) TAR (of BED, BIGWIG, BW, NARROWPEAK)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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