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Series GSE43390 Query DataSets for GSE43390
Status Public on Mar 12, 2015
Title Pausing of RNA polymerase II regulates mammalian developmental potential
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Summary The remarkable capacity for pluripotency and self-renewal in embryonic stem cells (ESCs) requires a finely-tuned transcriptional circuitry wherein the genes and pathways that initiate differentiation are suppressed, but poised to respond rapidly to developmental signals. To elucidate transcriptional control in mouse ESCs in the naïve, ground state, we defined the distribution of engaged RNA polymerase II (Pol II) at high-resolution. We find that promoter-proximal pausing of Pol II is widespread at genes encoding signaling molecules that control ESC proliferation, differentiation and metabolism, but is not enriched at developmental control genes. Accordingly, ablation of the primary pause-inducing factor, NELF, causes proliferation defects, early embryonic lethality and dysregulation of critical ESC signaling pathways. Moreover, loss of NELF in ESCs causes resistance to cell fate commitment through dramatic attenuation of FGF/ERK activity. This work thus uncovers an unanticipated role for NELF-mediated pausing in establishing the responsiveness of ESCs to developmental cues.
Overall design RNA-seq, GRO-seq, and Start-RNA-seq from mouse embryonic stem cells (mESCs). For RNA-seq, two biological replicates are included for each of two treatment conditions; control, and 4-hydroxytamoxifen (4OHT) treated to ablate expression of NELF-B. For GRO-seq, data from two biological replicates of untreated mESCs are included. For Start-RNA-seq, three biological replicates are included for each of two treatment conditions; control and 4OHT.
Contributor(s) Williams LH, Fromm G, Gokey NG, Henriques T, Muse GW, Burkholder A, Fargo DC, Hu G, Adelman K
Citation(s) 25773599
Submission date Jan 09, 2013
Last update date May 15, 2019
Contact name Karen Adelman
Organization name Harvard Medical School
Department Biological Chemistry and Molecular Pharmacology
Street address 45 Shattuck St. LHRRB-201a
City Boston
State/province MA
ZIP/Postal code 02115
Country USA
Platforms (2)
GPL13112 Illumina HiSeq 2000 (Mus musculus)
GPL16417 Illumina MiSeq (Mus musculus)
Samples (12)
GSM1422163 Bl6_mESC_C2cells_2i_4OHT_RNA-seq_rep1
GSM1422164 Bl6_mESC_C2cells_2i_4OHT_RNA-seq_rep2
GSM1422165 Bl6_mESC_C2cells_2i_Ctrl_RNA-seq_rep1
BioProject PRJNA185812
SRA SRP043635

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Supplementary file Size Download File type/resource
GSE43390_Adelman_Bl6_mESC_C2cells_2i_4OHT_startRNA-seq_5pr_allReps_norm_forward.bedgraph.gz 8.9 Mb (ftp)(http) BEDGRAPH
GSE43390_Adelman_Bl6_mESC_C2cells_2i_4OHT_startRNA-seq_5pr_allReps_norm_reverse.bedgraph.gz 8.7 Mb (ftp)(http) BEDGRAPH
GSE43390_Adelman_Bl6_mESC_C2cells_2i_Ctrl_startRNA-seq_5pr_allReps_norm_forward.bedgraph.gz 10.4 Mb (ftp)(http) BEDGRAPH
GSE43390_Adelman_Bl6_mESC_C2cells_2i_Ctrl_startRNA-seq_5pr_allReps_norm_reverse.bedgraph.gz 10.3 Mb (ftp)(http) BEDGRAPH 546.2 Mb (ftp)(http) BW 563.5 Mb (ftp)(http) BW
GSE43390_Bl6_mESC_C2cells_2i_GRO-seq_rep1and2_forward.bedgraph.gz 55.5 Mb (ftp)(http) BEDGRAPH
GSE43390_Bl6_mESC_C2cells_2i_GRO-seq_rep1and2_reverse.bedgraph.gz 54.2 Mb (ftp)(http) BEDGRAPH
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