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Acetylation and alternative splicing regulate ZNF76-mediated transcription
1Department of Pharmacology and Cancer Center, School of Medicine, Case Western Reserve University, Cleveland, OH 44106, USA.
Biochemical and Biophysical Research Communications
|December 13, 2005
Summary
Zinc Finger 76 (ZNF76) protein activity is controlled by acetylation and sumoylation, which have opposing effects. Alternative splicing also generates ZNF76 isoforms with varying TATA-binding protein interaction abilities.
Area of Science:
- Molecular Biology
- Gene Regulation
- Protein Biochemistry
Background:
- Zinc Finger 76 (ZNF76) functions as a general transcription repressor.
- ZNF76 targets the TATA-binding protein (TBP) and its activity is modulated by sumoylation.
Purpose of the Study:
- To identify additional regulatory mechanisms controlling ZNF76 function.
- To investigate the interplay between ZNF76 post-translational modifications and alternative splicing.
Main Methods:
- Investigated ZNF76 acetylation by p300 and deacetylation by HDAC1.
- Analyzed the impact of acetylation on ZNF76 sumoylation and TBP interaction.
- Examined the functional consequences of ZNF76 alternative splicing on TBP binding.
Main Results:
- ZNF76 undergoes acetylation by p300 and deacetylation by HDAC1.
- Acetylation of ZNF76 inhibits its sumoylation and reduces its interaction with TBP.
- Acetylation and sumoylation exhibit antagonistic roles in ZNF76 transactivation.
- Two ZNF76 isoforms generated by alternative splicing display differential TBP-binding affinities.
Conclusions:
- ZNF76, a TBP-interacting transcriptional modulator, is subject to regulation by both lysine modifications (acetylation and sumoylation) and alternative mRNA splicing.
- These regulatory mechanisms provide distinct layers of control over ZNF76's role in gene transcription.