|
| 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.
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| 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
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| |
|
| Contributor(s) |
Chin K |
| Citation(s) |
23086925 |
| |
| Submission date |
Oct 27, 2011 |
| Last update date |
May 15, 2019 |
| Contact name |
Keh-chuang Chin |
| E-mail(s) |
[email protected]
|
| 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)
|
| GSM823381 |
PolIISer2_JQ1treated_Tcell_ChIPseq |
| GSM823382 |
BRD4_untreated_hESC_ChIPseq |
| GSM823383 |
mRNA_untreated_Tcell_RNAseq |
| GSM1022942 |
mRNA_JQ1treated_Tcell_RNAseq |
| GSM1022943 |
BRD4_untreated_Tcell_ChIPseq_pooled5donor |
| GSM1022944 |
BRD4_JQ1treated_Tcell_ChIPseq_pooled5donor |
| GSM1022945 |
PolII4H8_untreated_Tcell_ChIPseq_pooled5donor |
| GSM1022946 |
PolII4H8_JQ1treated_Tcell_ChIPseq_pooled5donor |
| GSM1022947 |
PolIISer2_untreated_Tcell_ChIPseq_pooled5donor |
| GSM1022948 |
PolIISer2_JQ1treated_Tcell_ChIPseq_pooled5donor |
| GSM1022949 |
PolIISer5_untreated_Tcell_ChIPseq_pooled5donor |
| GSM1022950 |
PolIISer5_JQ1treated_Tcell_ChIPseq_pooled5donor |
|
| Relations |
| SRA |
SRP009105 |
| BioProject |
PRJNA149083 |
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