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| Status |
Public on Sep 03, 2019 |
| Title |
Endogenous interaction profiling identifies DDX5 as an oncogenic coactivator of transcription factor Fra-1 [ChIP-seq] |
| Organism |
Homo sapiens |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
|
| Summary |
Fra-1, a member of the activator protein 1 (AP-1) family, is overexpressed in triple-negative breast cancer (TNBC) and plays crucial roles in tumor progression. However, a systematic analysis of the composition of the Fra-1 protein network specifically on chromatin is still missing. Here we performed endogenous purification of Fra-1 transcriptional complex under ChIP conditions, followed by mass spectrometry, to identify chromatin-bound partners of Fra-1 in TNBC cells. This study allowed the identification of 118 interactors, highlighting DDX5 as the high ranking of Fra-1 interacting proteins. DDX5, a previously unrecognized protein in the network, is recruited globally to Fra-1 binding sites and shares a substantial set of Fra-1 target genes required for the TNBC cell growth. We provide evidence that DDX5 expression enhances Fra-1 transcriptional activity, thereby enhancing Fra-1-driven tumorigenesis. By integrating ChIP-seq and RNA-seq, we show that DDX5 target gene signature predicts poor clinical outcome in breast cancer patients. DDX5 protein level was higher in triple-negative basal like tumors than in non-basal like tumors, including luminal A, luminal B and HER2-enriched subtypes. Collectively, this comprehensive Fra-1 interaction profiling provides a broad and deep view of Fra-1 chromatin interaction landscape, which will help in deciphering mechanisms of AP-1 regulation of gene expression.
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| Overall design |
Identifiation of Fra-1 and DDX5 specific and common binding events in BT549 cells.
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| Web link |
https://www.nature.com/articles/s41388-019-0824-4
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| |
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| Contributor(s) |
He H, Song D, Sinha I, Hessling B, Li X, Haldosén L, Zao C |
| Citation(s) |
31015574 |
| |
| Submission date |
Apr 11, 2018 |
| Last update date |
Sep 05, 2019 |
| Contact name |
Karin Dahlman-Wright |
| Organization name |
Karolinska Institutet
|
| Department |
Department of Biosciences and Nutrition
|
| Lab |
Medicinaren 25/Neo
|
| Street address |
Blickagången 16
|
| City |
Huddinge |
| ZIP/Postal code |
14157 |
| Country |
Sweden |
| |
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| Platforms (1) |
| GPL11154 |
Illumina HiSeq 2000 (Homo sapiens) |
|
| Samples (4)
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| This SubSeries is part of SuperSeries: |
| GSE112963 |
Endogenous interaction profiling identifies DDX5 as an oncogenic coactivator of transcription factor Fra-1 |
|
| Relations |
| BioProject |
PRJNA449622 |
| SRA |
SRP139508 |
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