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Published on: August 26, 2012
Transcription factor IIB acetylates itself to regulate transcription
Chu H Choi1, Makoto Hiromura, Anny Usheva
1Endocrinology Division, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, 99 Brookline Avenue, Boston, Massachusetts 02215, USA.
Nature
|August 22, 2003
Summary
General transcription factor TFIIB undergoes acetylation, a post-translational modification. This autoacetylation stabilizes interactions and activates basal transcription, linking acetyl-CoA to gene regulation.
Area of Science:
- Molecular Biology
- Gene Regulation
- Biochemistry
Background:
- Acetylation is a known regulatory post-translational modification.
- The role of acetylation in regulating basal transcription factors remains largely unexplored.
- General transcription factors are crucial for initiating eukaryotic transcription.
Purpose of the Study:
- To investigate the role of acetylation in the regulation of basal transcription factors.
- To determine if TFIIB (general transcription factor II B) is subject to acetylation.
- To elucidate the functional consequences of TFIIB acetylation.
Main Methods:
- Biochemical assays to detect and characterize TFIIB acetylation.
- In vitro transcription assays using recombinant and cellular TFIIB.
- Site-directed mutagenesis to create non-acetylatable TFIIB mutants (K238A).
- Analysis of TFIIB-TFIIF interactions.
Main Results:
- TFIIB is acetylated at a specific lysine residue (K238).
- TFIIB possesses autoacetyltransferase activity, utilizing acetyl-CoA.
- Acetylation stabilizes the interaction between TFIIB and TFIIF.
- TFIIB autoacetylation enhances basal transcription initiation both in vitro and in cells.
- A non-acetylatable K238A mutant of TFIIB fails to activate transcription.
Conclusions:
- TFIIB acetylation is a novel regulatory mechanism for basal transcription.
- TFIIB acts as an autoacetyltransferase, linking acetyl-CoA to transcription.
- Acetylation of TFIIB plays a critical role in stabilizing transcription factor interactions and promoting gene expression.
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