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23086925
Bromodomain-containing protein 4 (BRD4) regulates RNA polymerase II serine 2 phosphorylation in human CD4+ T cells.

J Biol Chem, 2012/12/14;287(51):43137-55.

Zhang W[1], Prakash C, Sum C, Gong Y, Li Y, Kwok JJ, Thiessen N, Pettersson S, Jones SJ, Knapp S, Yang H, Chin KC

Affiliations

PMID: 23086925DOI: 10.1074/jbc.M112.413047

Impact factor: 5.486

Abstract
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 Ser-2-phosphorylated Pol II (Pol II Ser-2) 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 Ser-2, and reduced expression of lineage-specific genes in primary human CD4+ T cells. A large number of JQ1-disrupted BRD4 binding regions exhibited diacetylated 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.
MeSH terms
Acetylation; Binding Sites; CD4-Positive T-Lymphocytes; Cell Cycle Proteins; Cell Lineage; Embryonic Stem Cells; Enhancer Elements, Genetic; Genome, Human; HeLa Cells; Histone Acetyltransferases; Histone Deacetylases; Histones; Humans; Jurkat Cells; Lysine; Nuclear Proteins; Phosphorylation; Phosphoserine; Positive Transcriptional Elongation Factor B; Promoter Regions, Genetic; Protein Binding; Protein Transport; RNA Polymerase II; Transcription Factors; Transcription, Genetic
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