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| Status |
Public on Jan 19, 2017 |
| Title |
Cooperative binding of Oct4, Sox2, and Klf4 with stage-specific transcription factors orchestrates reprogramming [RNA-seq] |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Oct4, Sox2, Klf4, and cMyc (OSKM) reprogram somatic cells to pluripotency. To gain a mechanistic understanding of their function, we mapped OSKM-binding, stage-specific transcription-factors (TFs), and chromatin-states in discrete reprogramming stages and performed loss- and gain-of-function experiments. We found that early in reprogramming OSK extensively bind somatic-enhancers and initiate their decommissioning by recruiting Hdac1. Concurrently, OSK engage other sites, including specific pluripotency-enhancers, and induce the relocation of somatic TFs to these sites and away from somatic-enhancers, extending somatic-enhancer decommissioning genome-wide. Pluripotency-enhancer selection early in reprogramming occurs predominantly at sites with high OSK-motif densities and requires collaborative binding by OSK. Most pluripotency-enhancers are selected later and occupied by OS and stage-specific-TFs like Esrrb. Overexpression of stage-specific-TFs influences reprogramming efficiency by changing OSK-occupancy, somatic-enhancer decommissioning, and pluripotency-enhancer selection. We propose that collaborative interactions among OSK and with stage-specific-TFs direct both somatic-enhancer decommissioning and pluripotency-enhancer selection, which drives the enhancer reorganization underlying reprogramming
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| Overall design |
RNA-seq
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| Contributor(s) |
Chronis C, Fiziec P, Papp B, Butz S, Bonora G, Sabri S, Ernst J, Plath K |
| Citation(s) |
28111071 |
| Submission date |
Dec 05, 2016 |
| Last update date |
Dec 18, 2020 |
| Contact name |
Kathrin Plath |
| Organization name |
UCLA
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| Department |
Biological Chemistry
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| Lab |
BSRB 390B
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| Street address |
615 Charles E. Young Drive South
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| City |
Los Angeles |
| State/province |
CA |
| ZIP/Postal code |
90095-1737 |
| Country |
USA |
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| Platforms (1) |
| GPL9185 |
Illumina Genome Analyzer (Mus musculus) |
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| Samples (22)
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| This SubSeries is part of SuperSeries: |
| GSE90895 |
Cooperative binding of Oct4, Sox2, and Klf4 with stage-specific transcription factors orchestrates reprogramming |
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| Relations |
| BioProject |
PRJNA356298 |
| SRA |
SRP094578 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE90894_RPKM_mRNAseq_table.xlsx |
3.7 Mb |
(ftp)(http) |
XLSX |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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