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EBNA-1, a bifunctional transcriptional activator.
1McArdle Laboratory for Cancer Research, University of Wisconsin-Madison, Madison, Wisconsin 53706, USA.
Molecular and Cellular Biology
|September 16, 2003
Summary
Epstein-Barr nuclear antigen 1 (EBNA-1) activates transcription from integrated templates, a function distinct from its action on transfected DNA. This study identifies a specific EBNA-1 domain crucial for activating chromatin-embedded templates.
Area of Science:
- Molecular Biology
- Virology
- Epigenetics
Background:
- Transcription factors are identified using transient-transfection assays.
- Epstein-Barr nuclear antigen 1 (EBNA-1) activates transcription from transfected templates, but its effect on nuclear templates is debated.
Purpose of the Study:
- To investigate EBNA-1's transcriptional activation from integrated, chromatin-embedded templates.
- To genetically dissect the mechanism of EBNA-1's transcriptional activation.
Main Methods:
- Established cell lines with integrated EBNA-1-responsive templates.
- Performed mutational analysis of EBNA-1.
- Utilized dose-response experiments and inhibition assays.
Main Results:
- EBNA-1 dose-dependently activated transcription from integrated, chromatin-embedded templates.
- Identified an EBNA-1 domain essential for activating integrated templates but not transfected ones.
- A specific EBNA-1 derivative inhibited activation from integrated templates.
Conclusions:
- EBNA-1 activates transcription from integrated templates via a mechanism genetically distinct from its activation of transfected templates.
- A specific domain of EBNA-1 is critical for activating chromatin-embedded DNA.
- This finding clarifies EBNA-1's role in transcriptional regulation within its native chromatin environment.