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Bromodomain-Containing-Protein 4 (BRD4) Regulates RNA Polymerase II Serine 2 Phosphorylation in Human CD4+ T Cells

Poh Sheng Yeong1, Weishi Zhang1, Celine Prakash1, Calvin Sum1, Yue Gong1, Yinghui Li1, Jefferey Kwok1, Sven Pettersson2, Jones Steven3, Stefan Knapp4, Henry Yang1 and Keh Chuang Chin1*
  • 1 Singapore Immunology Network/ National University of Singapore, Singapore
  • 2 Karolinska Institutet, Department of Microbiology, Cell and Tumor Biology,, Sweden
  • 3 Bioinformatics Laboratory, Canada’s Michael Smith Genome Sciences Centre, Canada
  • 4 University of Oxford, United Kingdom

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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Keywords: BRD4, Ser2 Pol II, enhancers, gene tran, T cells

Conference: 15th International Congress of Immunology (ICI), Milan, Italy, 22 Aug - 27 Aug, 2013.

Presentation Type: Abstract

Topic: Immune receptors and signaling

Citation: Yeong P, Zhang W, Prakash C, Sum C, Gong Y, Li Y, Kwok J, Pettersson S, Steven J, Knapp S, Yang H and Chin K (2013). Bromodomain-Containing-Protein 4 (BRD4) Regulates RNA Polymerase II Serine 2 Phosphorylation in Human CD4+ T Cells. Front. Immunol. Conference Abstract: 15th International Congress of Immunology (ICI). doi: 10.3389/conf.fimmu.2013.02.00671

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Received: 12 Jun 2013; Published Online: 22 Aug 2013.

* Correspondence: Dr. Keh Chuang Chin, Singapore Immunology Network/ National University of Singapore, singapore, Singapore, kehchuang_chin@immunol.a-star.edu.sg