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Series GSE70449 Query DataSets for GSE70449
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.
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
Contributor(s) Follmer NE, Bryant BM, Mertz JA, Huang H, Chae M, Hatton C, Kraus WL, Sims III RJ
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Submission date Jul 01, 2015
Last update date Jan 07, 2023
Contact name Barbara M Bryant
Organization name Constellation Pharmaceuticals
Street address 215 First Street
City Cambridge
State/province MA
ZIP/Postal code 02142
Country USA
Platforms (1)
GPL16791 Illumina HiSeq 2500 (Homo sapiens)
Samples (6)
GSM1755009 LP-1_DMSO_10min_GRO-seq_rep1
GSM1755010 LP-1_500nM_JQ1_10min_GRO-seq_rep1
GSM1755011 LP-1_500nM_JQ1_30min_GRO-seq_rep1
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
BioProject PRJNA288702
SRA SRP060231

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

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)
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Raw data are available in SRA
Processed data are available on Series record
Processed data provided as supplementary file

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