Related Experiment Video
Updated: Dec 20, 2025
RNAscope for In situ Detection of Transcriptionally Active Human Papillomavirus in Head and Neck Squamous Cell Carcinoma
Published on: March 11, 2014
The viral oncogene human papillomavirus E7 deregulates transcriptional silencing by Brm-related gene 1 via molecular
Daeyoup Lee1, Chunghun Lim, Taegun Seo
1Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon 305-701, Korea.
Abstract:
BRG-1, a component of the human SWI/SNF complex, either activates or represses cellular promoters by modulating chromatin structure via the formation of a multiple polypeptide complex. Human papillomavirus E7 binds and destabilizes pRb, resulting in the blockage of G(1) arrest in the cell cycle. We show here that the high-risk human papillomavirus E7 protein group binds BRG-1 and modulates repression of the c-fos promoter mediated by this protein. In addition, both wild-type and Rb binding-defective E7 proteins abolish flat cell formation by BRG-1 in SW13 cells, whereas E7 COOH-terminal mutants do not affect this process. BRG-1-triggered repression of the c-fos promoter is sensitive to trichostatin A. We further establish that BRG-1 contains an activation domain and a trichostatin A-sensitive repression domain. These results collectively suggest that the viral oncogene E7 targets both pRb and BRG-1 via protein-protein interactions, resulting in the deregulation of host cell cycle control.
Insights
High-risk human papillomavirus E7 protein binds BRG-1, a SWI/SNF complex component, affecting cell cycle control. This interaction disrupts normal cell processes, highlighting viral oncogene targeting of host cell machinery.
Area of Science:
- Molecular Biology
- Cell Biology
- Virology
Background:
- BRG-1 is a key component of the human SWI/SNF complex, regulating gene expression through chromatin remodeling.
- The human papillomavirus (HPV) E7 protein is known to bind and destabilize retinoblastoma protein (pRb), disrupting cell cycle G1 arrest.
Purpose of the Study:
- To investigate the interaction between HPV E7 and BRG-1.
- To determine the functional consequences of E7 binding to BRG-1 on gene regulation and cell phenotype.
Main Methods:
- Co-immunoprecipitation assays to detect protein-protein interactions.
- Reporter gene assays to assess promoter activity (c-fos).
- Cell culture experiments (SW13 cells) to observe phenotypic changes (flat cell formation).
- Treatment with trichostatin A to evaluate drug sensitivity of repression domains.
Main Results:
- High-risk HPV E7 protein directly binds to BRG-1.
- HPV E7 modulates BRG-1-mediated repression of the c-fos promoter.
- Both wild-type and Rb-binding-defective E7 proteins abolish BRG-1-induced flat cell formation in SW13 cells.
- BRG-1-mediated repression of c-fos is sensitive to trichostatin A, indicating a histone deacetylase-dependent mechanism.
- BRG-1 possesses both an activation domain and a trichostatin A-sensitive repression domain.
Conclusions:
- Viral oncogene E7 targets both pRb and BRG-1 through protein-protein interactions.
- These interactions lead to the deregulation of host cell cycle control.
- The findings provide insight into the mechanisms by which HPV contributes to cellular transformation.
