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A dynamic model for PC4 coactivator function in RNA polymerase II transcription
S Malik1, M Guermah, R G Roeder
1Laboratory of Biochemistry and Molecular Biology, The Rockefeller University, 1230 York Avenue, New York, NY 10021, USA.
Summary
Human positive cofactor (PC4) requires TFIID and TFIIH for coactivator function in transcription. It represses initiation with minimal complexes but promotes their formation, highlighting a stepwise activation process.
Area of Science:
- Molecular Biology
- Gene Regulation
- Biochemistry
Background:
- Positive cofactor (PC4) is a general coactivator for RNA polymerase II transcription.
- PC4's role in activator-dependent transcription is established.
Purpose of the Study:
- To investigate the requirements for PC4 coactivator function.
- To elucidate the mechanism by which PC4 regulates transcription initiation.
Main Methods:
- Investigated PC4's dependence on TATA binding protein (TBP)-associated factors (TAFs) and TFIIH.
- Assessed PC4's effect on transcription initiation by minimal preinitiation complexes.
- Examined phosphorylation of PC4 by TFIIH and TAFII250.
Main Results:
- PC4 coactivator function requires TAFs in TFIID and TFIIH.
- PC4 represses transcription initiation by minimal complexes lacking TAFs/TFIIH while promoting their formation.
- TFIIH and TAFII250 phosphorylate PC4.
Conclusions:
- PC4 induces an inactive intermediate in preinitiation complex assembly.
- TFIIH and TAFs are essential for progressing this intermediate to a functional state.
- PC4 coactivator activity involves a stepwise mechanism similar to prokaryotic activation.