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E2F family members are differentially regulated by reversible acetylation
G Marzio1, C Wagener, M I Gutierrez
1Molecular Medicine Laboratory, International Centre for Genetic Engineering and Biotechnology, Area Science Park, Padriciano 99, 34012 Trieste, Italy.
The Journal of Biological Chemistry
|February 7, 2001
Summary
Transcription factors E2F-1, -2, and -3 are acetylated by p300 and CBP, enhancing their DNA binding and gene activation. This acetylation is reversible, suggesting a new regulatory mechanism for non-histone proteins.
Area of Science:
- Molecular Biology
- Cell Biology
- Epigenetics
Background:
- The E2F family of transcription factors regulates cell cycle progression and gene expression.
- E2F-1, -2, and -3 form a distinct subfamily with unique functional roles.
Purpose of the Study:
- To investigate the post-translational modification of E2F transcription factors.
- To determine the role of acetylation in the function of E2F-1, -2, and -3.
Main Methods:
- Co-immunoprecipitation assays to detect protein interactions.
- In vitro and in vivo acetylation assays.
- Electrophoretic mobility shift assays (EMSAs) to assess DNA binding affinity.
- Reporter gene assays to measure promoter transactivation.
Main Results:
- E2F-1, -2, and -3, but not E2F-4, -5, or -6, associate with and are acetylated by p300 and CBP.
- Acetylation occurs at conserved lysine residues within the DNA-binding domain.
- Acetylation significantly enhances E2F-1 binding affinity to DNA and promoter transactivation.
- Histone deacetylase 1 (HDAC1) can reverse the acetylation of E2F-1.
Conclusions:
- Acetylation is a key regulatory mechanism for E2F-1, -2, and -3 activity.
- Reversible acetylation modulates the DNA-binding and transcriptional activity of E2F transcription factors.
- This study reveals a novel layer of epigenetic regulation for non-histone proteins.