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Series GSE33281 Query DataSets for GSE33281
Status Public on Nov 14, 2012
Title Bromodomain-Containing-Protein 4 (BRD4) Regulates RNA Polymerase II Serine 2 Phosphorylation in Human CD4+ T Cells
Organism Homo sapiens
Experiment type Genome binding/occupancy profiling by high throughput sequencing
Expression profiling by high throughput sequencing
Summary Transcriptional elongation by RNA polymerase II (Pol II) is regulated by positive transcription elongation factor b (P-TEFb) in association with Bromodomain-containing protein 4 (BRD4). We used genome-wide chromatin immunoprecipitation sequencing in primary human CD4+ T cells to reveal that BRD4 co-localizes with Ser2-phosphorylated Pol II (Pol II Ser2) at both enhancers and promoters of active genes. Disruption of bromodomain:histone acetylation interactions by JQ1, a small-molecule bromodomain inhibitor, resulted in decreased BRD4 binding, reduced Pol II Ser2, and reduced expression of lineage-specific genes in primary human CD4+ T cells. A large number of JQ1-disrupted BRD4 binding regions exhibited di-acetylated H4 (lysine-5 and -8) and H3K27 acetylation (H3K27ac), which correlated with the presence of histone acetyltransferases and deacetylases. Genes associated with BRD4/H3K27ac co-occupancy exhibited significantly higher activity than those associated with H3K27ac or BRD4 binding alone. Comparison of BRD4 binding in T cells and in human embryonic stem cells revealed that enhancer BRD4 binding sites were predominantly lineage-specific. Our findings suggest that BRD4-driven Pol II phosphorylation at serine 2 plays an important role in regulating lineage-specific gene transcription in human CD4+ T cells.
Overall design Examination of BRD4, total Pol II, serine 2 phosphorylated Pol II and serine 5 phosphorylated Pol II binding in CD4+ T cells (with and without JQ1 treatment) and BRD4 binding in human embryonic stems cell; PolyA RNA expression in CD4+ T cells( with and without JQ1 treatment) using RNA-seq
Contributor(s) Chin K
Citation(s) 23086925
Submission date Oct 27, 2011
Last update date May 15, 2019
Contact name Keh-chuang Chin
Organization name Singapore Immunology Network
Department Laboratory of Gene Regulation
Street address Biopolis, 8A Biomedical Grove, #03-06 Immunos
City Singapore
ZIP/Postal code 138648
Country Singapore
Platforms (2)
GPL10999 Illumina Genome Analyzer IIx (Homo sapiens)
GPL11154 Illumina HiSeq 2000 (Homo sapiens)
Samples (15)
GSM823378 BRD4_untreated_Tcell_ChIPseq
GSM823379 BRD4_JQ1treated_Tcell_ChIPseq
GSM823380 PolII4H8_JQ1treated_Tcell_ChIPseq
SRA SRP009105
BioProject PRJNA149083

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Supplementary file Size Download File type/resource
GSE33281_RAW.tar 7.8 Gb (http)(custom) TAR (of BED, WIG)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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