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| Status |
Public on Apr 10, 2018 |
| Title |
DNA-binding pluripotency factors and DNA demethylases can cooperate to maintain pluripotent stem cell identity even in the absence of Brd4 [RNA-seq] |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Histone acetylation and the acetyl-lysine reader Brd4 have recently been implicated in embryonic stem cell (ESC) proliferation and self-renewal. We found that naïve pluripotent ESCs exhibit increased incorporation of glucose-derived carbons onto acetylated histones and elevations in H3K9ac and Brd4 recruitment at pluripotency gene promoters. Surprisingly, both H3K9 acetyltransferases, GCN5 and PCAF, and Brd4 recruitment were dispensable for proliferation, self-renewal and pluripotency of naïve ESCs. Naïve ESCs maintain gene expression by stabilizing Mediator at core pluripotency genes in a Brd4-independent manner. Brd4-independent proliferation could also be achieved in metastable ESCs by overexpression of pluripotency transcription factors. Under all conditions, self-renewal required the DNA methylcytosine oxidases Tet1 and Tet2. These data reveal that there is minimal dependence on Brd4 for self-renewal of naïve ESCs. Instead, the relative levels of DNA methylation and transcription factor abundance determine the requirement for bromodomain recognition of histone acetylation to the maintenance of stem cell identity.
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| Overall design |
RNA sequencing of murine embryonic stem cells maintained in media containing fetal bovine serum and leukemia inhibitory factor (LIF) with or without inhibitors of GSK3b and MEK ('2i') and treated for 72h with JQ1 or vehicle control.
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| Contributor(s) |
Finley LW, Vardhana S, Carey BW, King B, Allis CD, Thompson CB |
| Citation(s) |
29662175 |
| Submission date |
Oct 14, 2016 |
| Last update date |
Oct 03, 2019 |
| Contact name |
Bryan King |
| E-mail(s) |
kingb2@mskcc.org
|
| Organization name |
Memorial Sloan Kettering Cancer Center
|
| Department |
Cancer Biology and Genetics
|
| Lab |
Craig Thompson Lab
|
| Street address |
430 E 67th St RRL-469
|
| City |
New York |
| State/province |
NY |
| ZIP/Postal code |
10065 |
| Country |
USA |
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| Platforms (1) |
| GPL19057 |
Illumina NextSeq 500 (Mus musculus) |
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| Samples (12)
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| Relations |
| BioProject |
PRJNA348473 |
| SRA |
SRP091562 |
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