Bromodomain-containing protein 4 (BRD4) regulates RNA polymerase II serine 2 phosphorylation in human CD4+ T cells.
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-...
| Những tác giả chính: | , , , , , , , , , , , |
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| Định dạng: | Journal article |
| Ngôn ngữ: | English |
| Được phát hành: |
2013
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| _version_ | 1826265900666322944 |
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| author | Zhang, W Prakash, C Prakash, C Sum, C Sum, C Gong, Y Gong, Y Li, Y Li, Y Kwok, J Kwok, J Thiessen, N Thiessen, N Pettersson, S Pettersson, S Jones, S Jones, S Knapp, S Knapp, S Yang, H Yang, H Chin, K Chin, K |
| author_facet | Zhang, W Prakash, C Prakash, C Sum, C Sum, C Gong, Y Gong, Y Li, Y Li, Y Kwok, J Kwok, J Thiessen, N Thiessen, N Pettersson, S Pettersson, S Jones, S Jones, S Knapp, S Knapp, S Yang, H Yang, H Chin, K Chin, K |
| author_sort | Zhang, W |
| collection | OXFORD |
| description | 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. |
| first_indexed | 2024-03-06T20:30:49Z |
| format | Journal article |
| id | oxford-uuid:30f7bf9a-c9d6-4ea1-a48f-079820d8ba50 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T20:30:49Z |
| publishDate | 2013 |
| record_format | dspace |
| spelling | oxford-uuid:30f7bf9a-c9d6-4ea1-a48f-079820d8ba502022-03-26T13:05:01ZBromodomain-containing protein 4 (BRD4) regulates RNA polymerase II serine 2 phosphorylation in human CD4+ T cells.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:30f7bf9a-c9d6-4ea1-a48f-079820d8ba50EnglishSymplectic Elements at Oxford2013Zhang, WPrakash, CPrakash, CSum, CSum, CGong, YGong, YLi, YLi, YKwok, JKwok, JThiessen, NThiessen, NPettersson, SPettersson, SJones, SJones, SKnapp, SKnapp, SYang, HYang, HChin, KChin, KTranscriptional 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. |
| spellingShingle | Zhang, W Prakash, C Prakash, C Sum, C Sum, C Gong, Y Gong, Y Li, Y Li, Y Kwok, J Kwok, J Thiessen, N Thiessen, N Pettersson, S Pettersson, S Jones, S Jones, S Knapp, S Knapp, S Yang, H Yang, H Chin, K Chin, K Bromodomain-containing protein 4 (BRD4) regulates RNA polymerase II serine 2 phosphorylation in human CD4+ T cells. |
| title | Bromodomain-containing protein 4 (BRD4) regulates RNA polymerase II serine 2 phosphorylation in human CD4+ T cells. |
| title_full | Bromodomain-containing protein 4 (BRD4) regulates RNA polymerase II serine 2 phosphorylation in human CD4+ T cells. |
| title_fullStr | Bromodomain-containing protein 4 (BRD4) regulates RNA polymerase II serine 2 phosphorylation in human CD4+ T cells. |
| title_full_unstemmed | Bromodomain-containing protein 4 (BRD4) regulates RNA polymerase II serine 2 phosphorylation in human CD4+ T cells. |
| title_short | Bromodomain-containing protein 4 (BRD4) regulates RNA polymerase II serine 2 phosphorylation in human CD4+ T cells. |
| title_sort | bromodomain containing protein 4 brd4 regulates rna polymerase ii serine 2 phosphorylation in human cd4 t cells |
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