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Science 293 (5532): 1133-1136

Copyright © 2001 by the American Association for the Advancement of Science

Coordination of a Transcriptional Switch by HMGI(Y) Acetylation

Nikhil Munshi, Theodora Agalioti, Stavros Lomvardas, Menie Merika, Guoying Chen, Dimitris Thanos*

Dynamic control of interferon-beta (IFN-beta ) gene expression requires the regulated assembly and disassembly of the enhanceosome, a higher-order nucleoprotein complex formed in response to virus infection. The enhanceosome activates transcription by recruiting the histone acetyltransferase proteins CREB binding protein (CBP) and <UNL>p</UNL>300/<UNL>C</UNL>BP-<UNL>a</UNL>ssociated <UNL>f</UNL>actors (PCAF)/GCN5, which, in addition to modifying histones, acetylate HMGI(Y), the architectural component required for enhanceosome assembly. We show that the accurate execution of the IFN-beta transcriptional switch depends on the ordered acetylation of the high-mobility group I protein HMGI(Y) by PCAF/GCN5 and CBP, which acetylate HMGI(Y) at distinct lysine residues on endogenous promoters. Whereas acetylation of HMGI(Y) by CBP at lysine-65 destabilizes the enhanceosome, acetylation of HMGI(Y) by PCAF/GCN5 at lysine-71 potentiates transcription by stabilizing the enhanceosome and preventing acetylation by CBP.

Department of Biochemistry and Molecular Biophysics, Columbia University, 630 West 168th Street, New York, NY 10032, USA.
*   To whom correspondence should be addressed. E-mail: dt73{at}

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