Transcriptional switch

Transcription is regulated by the coordinated assembly of protein complexes that synergize to switch on gene expression. The virally induced enhanceosome of the interferon-β (IFN-β) gene is one of the best characterized transcriptional switches. In the August 10 Science, Nikhil Munshi and colleagues from Columbia University describe how acetylation of the architectural high-mobility-group protein HMGI(Y) regulates stability of the IFN-β enhanceosome (Science 2001, 293:1133-1136). The HMGI(Y) protein is a target for acetylation by two different enzymes (CBP and PCAF/GCN5) on distinct lysine residues (Lys65 and Lys71, respectively). Munshi et al. mutated Lys71 and observed decreased virus-induced transcription and reduced interaction with enhanceosome proteins. They propose that HMGI(Y) acetylation by PCAF/GCN5 facilitates enhanceosome assembly. They performed chromatin immunoprecipitation experiments to demonstrate that K71 acetylation coincides with enhanceosome assembly and activation (3 hours-post infection), whereas Lys65 acetylation occurred at the time of enhanceosome disruption (after 6 hours). Also, Lys71 acetylation decreased the efficiency of CBP acetylation on Lys65. Munshi et al. propose a model in which the ordered recruitment of, and acetylation by, PCAF/GCN5 followed by CBP regulates enhanceosome stability (assembly and disassembly, respectively) and the transcriptional switch.