Structure, function, and activator-induced conformations of the CRSP coactivator
Dylan J Taatjes1, Anders M Näär, Frank Andel
1Howard Hughes Medical Institute and, Lawrence Berkeley National Laboratory, Department of Molecular and Cell Biology, 401 Barker Hall, University of California, Berkeley, CA 94720, USA.
Science (New York, N.Y.)
|February 9, 2002
Summary
The activator-recruited cofactor (ARC) complex separates into two parts: ARC-L and the cofactor required for Sp1 activation (CRSP). CRSP is the active transcription cofactor, showing distinct conformations influenced by activators.
Area of Science:
- Molecular Biology
- Biochemistry
- Gene Regulation
Background:
- Human cofactor complexes ARC and CRSP are known to mediate activator-dependent transcription in vitro.
- The structural and functional relationship between ARC and CRSP, despite shared subunits, remains unclear.
Purpose of the Study:
- To investigate the structural and functional relationship between the ARC and CRSP cofactor complexes.
- To determine the individual roles of ARC subcomplexes in transcriptional regulation.
Main Methods:
- Affinity purification of ARC complex.
- Biochemical separation of ARC into ARC-L and CRSP subcomplexes.
- In vitro transcription assays.
- Electron microscopy (EM) and 3D reconstruction for structural analysis.
Main Results:
- Affinity-purified ARC comprises two distinct complexes: ARC-L and CRSP.
- CRSP is transcriptionally active, while ARC-L is inactive.
- EM analysis revealed significant structural differences between ARC-L and CRSP.
- CRSP exhibited distinct activator-induced conformations.
Conclusions:
- CRSP is the functional coactivator, distinct from the inactive ARC-L complex.
- Activator-induced conformational changes in CRSP are likely key to its transcriptional potentiation.
- This study clarifies the subunit composition and functional roles within the ARC/CRSP transcription machinery.
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