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| Status |
Public on Sep 15, 2011 |
| Title |
An Alternative Splicing Switch Regulates Embryonic Stem Cell Pluripotency and Reprogramming [protein binding microarray] |
| Platform organism |
synthetic construct |
| Sample organism |
Homo sapiens |
| Experiment type |
Other
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| Summary |
Alternative splicing (AS) is a key process underlying the expansion of proteomic diversity and the regulation of gene expression. However, the contribution of AS to the control of embryonic stem cell (ESC) pluripotency is not well understood. Here, we identify an evolutionarily conserved ESC-specific AS event that changes the DNA binding preference of the forkhead family transcription factor FOXP1. We show that the ESC-specific isoform of FOXP1 stimulates the expression of transcription factor genes required for pluripotency including OCT4, NANOG, NR5A2 and GDF3, while concomitantly repressing genes required for ESC differentiation. Remarkably, this isoform also promotes the maintenance of ESC pluripotency and the efficient reprogramming of somatic cells to induced pluripotent stem cells. These results reveal an AS switch that plays a pivotal role in the regulation of pluripotency through the control of critical ESC-specific transcriptional programs.
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| Overall design |
Protein binding microarray (PBM) experiments were performed for two isoforms of the DNA binding domain of the human FOXP1 gene. Briefly, the PBMs involved binding GST-tagged DNA-binding proteins to two double-stranded 4*44K Agilent microarrays, each containing a different DeBruijn sequence design, in order to determine their sequence preferences. The method is described in Berger et al., Nature Biotechnology 2006.
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| Contributor(s) |
Gabut M, Samavarchi-Tehrani P, Wang X, Slobodeniuc V, O’Hanlon D, Sung H, Alvarez M, Talukder S, Pan Q, Woltjen K, Mazzoni EO, Nedelec S, Wichterle H, Hughes TR, Zandstra P, Nagy A, Wrana JL, Blencowe BJ |
| Citation(s) |
21924763 |
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| Submission date |
Jul 28, 2011 |
| Last update date |
Jun 10, 2014 |
| Contact name |
Xinchen Wang |
| E-mail(s) |
xinchenw@mit.edu
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| Organization name |
MIT
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| Street address |
32 Vassar St, D514
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| City |
Cambridge |
| State/province |
MA |
| ZIP/Postal code |
02139 |
| Country |
USA |
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| Platforms (1) |
| GPL11260 |
Agilent custom ME and HK design array [8mer] |
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| Samples (6)
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| This SubSeries is part of SuperSeries: |
| GSE30992 |
An Alternative Splicing Switch Regulates Embryonic Stem Cell Pluripotency and Reprogramming |
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| Relations |
| BioProject |
PRJNA154621 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE31007_RAW.tar |
8.5 Mb |
(http)(custom) |
TAR (of TXT) |
| Processed data included within Sample table |
| Processed data provided as supplementary file |
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