|
| Status |
Public on Jan 06, 2023 |
| Title |
BRD4 loading at the transcription start site mediates pause-release and underlies the disproportionate transcriptional response to BET bromodomain inhibition [GRO-Seq] |
| Organism |
Homo sapiens |
| Experiment type |
Other
Expression profiling by high throughput sequencing
|
| Summary |
BET bromodomain inhibition (BETi) abrogates cancer cell growth by disrupting oncogenic gene expression. BRD4 loading at enhancers has been suggested to mediate pause-release and underlie the selective transcriptional response to BETi. Here, we utilized GRO-seq coupled with ChIP-seq to assess the association between gene control elements and the transcriptional response to BETi. Genes immediately down-regulated by BETi display a marked pause-release defect with a minimal impact on transcript elongation within the gene body. Surprisingly, we find that BRD4 at super-enhancers does not render its associated genes or enhancer RNAs preferentially sensitive to BETi. In contrast, disproportionate loading of BRD4 at transcription start sites (TSS) correlates with the transcriptional response to BETi. Moreover, BRD4 loading at TSSs, but not enhancers, is associated with enhanced promoter-proximal pausing following BETi. Our findings stress a mechanistic role of promoter-associated BRD4 in pause-release and suggest that BRD4 loading at the TSS drives the selective transcriptional response to BETi.
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| Overall design |
LP-1 multiple myeloma cell line was treated with DMSO or 0.5 μM JQ1 for 10 min, or with 0.5 μM JQ1 for 30 min and then anyzed by GRO-Seq
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| Contributor(s) |
Follmer NE, Bryant BM, Mertz JA, Huang H, Chae M, Hatton C, Kraus WL, Sims III RJ |
| Citation missing |
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| Submission date |
Jul 01, 2015 |
| Last update date |
Jan 07, 2023 |
| Contact name |
Barbara M Bryant |
| E-mail(s) |
barbara.bryant@constellationpharma.com
|
| Organization name |
Constellation Pharmaceuticals
|
| Street address |
215 First Street
|
| City |
Cambridge |
| State/province |
MA |
| ZIP/Postal code |
02142 |
| Country |
USA |
| |
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| Platforms (1) |
| GPL16791 |
Illumina HiSeq 2500 (Homo sapiens) |
|
| Samples (6)
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| This SubSeries is part of SuperSeries: |
| GSE70450 |
BRD4 loading at the transcription start site mediates pause-release and underlies the disproportionate transcriptional response to BET bromodomain inhibition |
|
| Relations |
| BioProject |
PRJNA288702 |
| SRA |
SRP060231 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE70449_GRO-seq_expression.txt.gz |
2.7 Mb |
(ftp)(http) |
TXT |
| GSE70449_GRO-seq_pausing_indicies_BRD4_TSS_10min.txt.gz |
174.7 Kb |
(ftp)(http) |
TXT |
| GSE70449_GRO-seq_pausing_indicies_BRD4_enhancer_10min.txt.gz |
342.2 Kb |
(ftp)(http) |
TXT |
| GSE70449_GRO-seq_pausing_indicies_downregulated_10min.txt.gz |
92.5 Kb |
(ftp)(http) |
TXT |
| GSE70449_GRO-seq_pausing_indicies_downregulated_30min.txt.gz |
83.0 Kb |
(ftp)(http) |
TXT |
| GSE70449_GRO-seq_pausing_indicies_hiBRD4_TSS_10min.txt.gz |
18.6 Kb |
(ftp)(http) |
TXT |
| GSE70449_GRO-seq_pausing_indicies_loBRD4_TSS_10min.txt.gz |
239.3 Kb |
(ftp)(http) |
TXT |
| GSE70449_GRO-seq_pausing_indicies_noBRD4_TSS_10min.txt.gz |
349.2 Kb |
(ftp)(http) |
TXT |
| GSE70449_GRO-seq_pausing_indicies_noBRD4_enhancer_10min.txt.gz |
267.2 Kb |
(ftp)(http) |
TXT |
| GSE70449_GRO-seq_pausing_indicies_super-enhancer_10min.txt.gz |
24.1 Kb |
(ftp)(http) |
TXT |
| GSE70449_GRO-seq_pausing_indicies_typical_enhancer_10min.txt.gz |
207.6 Kb |
(ftp)(http) |
TXT |
| GSE70449_GRO-seq_pausing_indicies_unaffected_10min.txt.gz |
427.0 Kb |
(ftp)(http) |
TXT |
| GSE70449_GRO-seq_pausing_indicies_unaffected_30min.txt.gz |
433.3 Kb |
(ftp)(http) |
TXT |
| GSE70449_GRO-seq_signal_at_enhancers.txt.gz |
1.0 Mb |
(ftp)(http) |
TXT |
| GSE70449_RAW.tar |
1.1 Gb |
(http)(custom) |
TAR (of WIG) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
| Processed data provided as supplementary file |
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