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Series GSE88760 Query DataSets for GSE88760
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
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.
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.
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
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
Platforms (1)
GPL19057 Illumina NextSeq 500 (Mus musculus)
Samples (12)
GSM2345133 SL_veh_1
GSM2345134 SL_veh_2
GSM2345135 SL_veh_3
BioProject PRJNA348473
SRA SRP091562

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GSE88760_normalized_gene_counts.txt.gz 1.5 Mb (ftp)(http) TXT
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