Transcriptional switch

Ordered acetylation of the HMGI(Y) protein controls enhanceosome stability and switches on gene expression.

Jonathan Weitzman(

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...

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