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| Status |
Public on Dec 06, 2013 |
| Title |
ChIP-seq analysis of PHF20 and Wdr5 binding sites in ESCs |
| Organism |
Mus musculus |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
|
| Summary |
Although reprogramming of somatic cells to generate inducible pluripotent stem cells (iPSCs) is associated with remarkable epigenetic changes, the role and mechanisms of epigenetic factors in this process remains poorly understood. Here we describe identification of Jmjd3 as a potent negative regulator of reprogramming. Jmjd3-deficient MEFs produced significantly more iPSC colonies than did wild-type cells, while ectopic expression of Jmjd3 markedly inhibited reprogramming. We further show that the inhibitory effects of Jmjd3 are produced through both histone demethylase-dependent and -independent pathways acting in concert. The latter pathway is entirely novel and involved Jmjd3 targeting of PHF20 for ubiquitination and degradation by recruiting an E3 ligase Trim26. Importantly, PHF20-deficient MEFs could not be converted to fully reprogrammed iPSCs, even with knockdown of Jmjd3, Ink4a or p21, indicating dominant effects of this protein on reprogramming. Our findings identify a previously unrecognized role of Jmjd3 in reprogramming and provide molecular insight into the mechanisms by which the Jmjd3-PHF20 axis controls the reprogramming process.
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| Overall design |
This study was an examination of phf20 and wdr5 binding patterns in embryonic stem cells, using a ChIP-Sequencing methodology with antibodies for each of these factors in the cell lines indicated.
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| Contributor(s) |
Wang R, Zhao W, Ayers S |
| Citation(s) |
23452852 |
| |
| Submission date |
Jan 02, 2013 |
| Last update date |
May 15, 2019 |
| Contact name |
Stephen D Ayers |
| E-mail(s) |
sda6@cornell.edu
|
| Phone |
713-441-8693
|
| Fax |
713-793-7162
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| URL |
http://www.methodisthealth.com/stephen-ayers-phd
|
| Organization name |
Methodist Hospital Research Institute
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| Department |
Genomic Medicine
|
| Lab |
Genomic Medicine
|
| Street address |
6565 Fannin Street F8-060
|
| City |
Houston |
| State/province |
Texas |
| ZIP/Postal code |
77030 |
| Country |
USA |
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| Platforms (1) |
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| Samples (8)
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| Relations |
| BioProject |
PRJNA185142 |
| SRA |
SRP017726 |
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