RNAs interact with BRD4 to promote enhanced chromatin engagement and transcription activation
| Autor: | Zhengxi Sun, Homa Rahnamoun, Kristen M. Ramsey, Shannon M. Lauberth, Jihoon Lee, Elizabeth A. Komives, Hanbin Lu |
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| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
Transcriptional Activation
0301 basic medicine BRD4 Enhancer Elements 1.1 Normal biological development and functioning Biophysics Cell Cycle Proteins Plasma protein binding Medical and Health Sciences Article Histones 03 medical and health sciences Genetic Protein Domains Structural Biology Genetics 2.1 Biological and endogenous factors Humans Enhancer Molecular Biology Cancer Regulation of gene expression biology Chemistry Nuclear Proteins Acetylation Promoter Biological Sciences Chromatin Bromodomain Cell biology Enhancer Elements Genetic 030104 developmental biology Histone Chemical Sciences biology.protein RNA Generic health relevance Tumor Suppressor Protein p53 Transcription Factors Signal Transduction Protein Binding Developmental Biology |
| Zdroj: | Rahnamoun, Homa; Lee, Jihoon; Sun, Zhengxi; Lu, Hanbin; Ramsey, Kristen M; Komives, Elizabeth A; et al.(2018). RNAs interact with BRD4 to promote enhanced chromatin engagement and transcription activation.. Nature structural & molecular biology, 25(8), 687-697. doi: 10.1038/s41594-018-0102-0. UC San Diego: Retrieved from: http://www.escholarship.org/uc/item/0693t1gv Nature structural & molecular biology, vol 25, iss 8 |
| DOI: | 10.1038/s41594-018-0102-0. |
| Popis: | Bromodomain and extra-terminal motif (BET) protein BRD4 binds to acetylated histones at enhancers and promoters through its bromodomains (BDs) to regulate transcriptional elongation. Here, we reveal in human colorectal cancer cells that BRD4 is recruited to enhancers that are co-occupied by mutant p53 and support the synthesis of enhancer-directed transcripts (eRNAs) in response to chronic immune signaling. We identify that BRD4 selectively associates with eRNAs that are produced from BRD4 bound enhancers. Through biochemical and biophysical characterizations, we show that BRD4 BDs function cooperatively as docking sites for eRNAs and that the BDs of BRD2, BRD3, BRDT, BRG1, and BRD7 directly interact with eRNAs. BRD4-eRNA interactions increase BRD4 binding to acetylated histones and promote enhanced BRD4 recruitment at specific enhancers which augments BRD4 transcriptional activities. This work highlights a mechanism by which eRNAs play a direct role in gene regulation by modulating enhancer interactions and transcriptional functions of BRD4. |
| Databáze: | OpenAIRE |
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