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Adenovirus E1A proteins interact with the cellular YY1 transcription factor
1Department of Molecular Biology, Howard Hughes Medical Institute, Princeton University, New Jersey 08544-1014.
Journal of Virology
|March 1, 1995
Summary
Adenovirus E1A proteins bind to the transcription factor YY1, relieving repression. The 13S E1A variant binds more strongly and activates transcription, suggesting E1A directly interacts with YY1 to regulate gene expression.
Area of Science:
- Molecular Biology
- Virology
- Gene Regulation
Background:
- Adenovirus E1A proteins are known to modulate cellular transcription.
- The cellular transcription factor YY1 can repress gene expression.
- Previous studies suggest E1A proteins can relieve YY1-mediated repression.
Purpose of the Study:
- To investigate the interaction between adenovirus E1A proteins and the transcription factor YY1.
- To identify the domains involved in E1A-YY1 binding and functional consequences.
- To elucidate the mechanism by which E1A relieves YY1-mediated transcriptional repression.
Main Methods:
- In vivo and in vitro binding assays to assess E1A-YY1 interaction.
- Site-directed mutagenesis to map interaction domains on E1A and YY1.
- Reporter gene assays to evaluate transcriptional activity and repression relief.
- Cotransfection experiments using GAL4-YY1 fusion proteins.
Main Results:
- Both 12S and 13S E1A proteins bind to YY1, with 13S E1A showing higher affinity.
- Specific domains on E1A (N-terminal and CR3) and YY1 (residues 54-260 and C-terminal 332-414) mediate the interaction.
- E1A interaction with the YY1 C-terminal domain correlates with relief of repression.
- E1A proteins can relieve repression mediated by the carboxy-terminal domain of YY1.
Conclusions:
- Adenovirus E1A proteins directly bind to the transcription factor YY1.
- The interaction involves specific domains on both E1A and YY1 proteins.
- E1A proteins relieve YY1-mediated transcriptional repression, at least in part, through direct binding to YY1.