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| Status |
Public on Oct 23, 2019 |
| Title |
Cancer-associated missense mutations enhance the pluripotency reprogramming activity of OCT4 and SOX17 |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
The functional consequences of cancer-associated missense mutations are unclear for majority of proteins, here we interrogated cancer mutation databases and identified recurrently mutated positions at structural contact interface of DNA-binding domains of SOX and POU family transcription factors. We used conversion of mouse embryonic fibroblasts (MEFs) to induced pluripotent stem cells (iPSCs) as a functional read out. In this study we identified several gain-of-function mutations that enhance cellular pluripotency reprogramming by SOX2 and OCT4. Wild type SOX17 does not support pluripotency reprogramming while recurrent missense mutation SOX17-V118M converts SOX17 into a pluripotency inducer, viability of cancer cells and provides protein stability. Here, we conclude that mutational profile of SOX and OCT family factors in cancer association can give direction to design high-performance reprogramming factors.
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| Overall design |
We analyzed the gene expression profiles of SOX17WT and SOX17-V118M mutant that is a recurrent mutation lies at contact interface of SOX/OCT heterodimer leading to a increased cooperativity binding in the presence of compressed motif “CATTGTATGCAAAT” DNA element. Moreover, SOX17-V118M is an inducer to pluripotency and this mutation convert non reprogramming SOX17 to reprogramming SOX17 factor. Data in GEO is submitted by name SOX17-V118M, gene expression profile at day 9 somatic cell reprogramming of SOX17WT and SOX17-V118M done by RNA-seq.
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| Web link |
https://febs.onlinelibrary.wiley.com/doi/full/10.1111/febs.15076
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| Contributor(s) |
Srivastava Y, Malik V, Jauch R |
| Citation(s) |
31569299 |
| |
| Submission date |
Jul 26, 2019 |
| Last update date |
Oct 23, 2019 |
| Contact name |
YOGESH SRIVASTAVA |
| E-mail(s) |
[email protected]
|
| Phone |
15622320973
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| Organization name |
Guangzhou Institutes of Biomedicine and Health
|
| Department |
Biochemistry and Molecular Biology
|
| Lab |
Genome Regulation
|
| Street address |
190 Kaiyuan Avenue
|
| City |
Guangzhou |
| State/province |
Guangdong |
| ZIP/Postal code |
510530 |
| Country |
China |
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| Platforms (1) |
| GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
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| Samples (4)
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| Relations |
| BioProject |
PRJNA556845 |
| SRA |
SRP216490 |
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