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Science 295 (5557): 1058-1062

Copyright © 2002 by the American Association for the Advancement of Science

Structure, Function, and Activator-Induced Conformations of the CRSP Coactivator

Dylan J. Taatjes,1 Anders M. Näär,1 Frank Andel III,12 Eva Nogales,12 Robert Tjian1*

The human cofactor complexes ARC (activator-recruited cofactor) and CRSP (cofactor required for Sp1 activation) mediate activator-dependent transcription in vitro. Although these complexes share several common subunits, their structural and functional relationships remain unknown. Here, we report that affinity-purified ARC consists of two distinct multisubunit complexes: a larger complex, denoted ARC-L, and a smaller coactivator, CRSP. Reconstituted in vitro transcription with biochemically separated ARC-L and CRSP reveals differential cofactor functions. The ARC-L complex is transcriptionally inactive, whereas the CRSP complex is highly active. Structural determination by electron microscopy (EM) and three-dimensional reconstruction indicate substantial differences in size and shape between ARC-L and CRSP. Moreover, EM analysis of independently derived CRSP complexes reveals distinct conformations induced by different activators. These results suggest that CRSP may potentiate transcription via specific activator-induced conformational changes.

1 Howard Hughes Medical Institute and
2 Lawrence Berkeley National Laboratory, Department of Molecular and Cell Biology, 401 Barker Hall, University of California, Berkeley, CA 94720, USA.
*   To whom correspondence should be addressed. E-mail: jmlim{at}uclink4.berkeley.edu



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