Structure and ligand of a histone acetyltransferase bromodomain.
Dhalluin, Christophe; Carlson, Justin E.; Zeng, Lei; He, Cheng; Aggarwal, Aneel K.; Zhou, Ming-Ming
[Letter] Nature. 399(6735):491-496, June 3, 1999.

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Histone acetylation is important in chromatin remodelling and gene activation *RF 1-4*. Nearly all known histone-acetyltransferase (HAT)-associated transcriptional co-activators contain bromodomains, which are [approximate] 110-amino-acid modules found in many chromatin-associated proteins [5-9]. Despite the wide occurrence of these bromodomains, their three-dimensional structure and binding partners remain unknown. Here we report the solution structure of the bromodomain of the HAT co-activator P/CAF (p300/CBP-associated factor) [10,11]. The structure reveals an unusual left-handed up-and-down four-helix bundle. In addition, we show by a combination of structural and site-directed mutagenesis studies that bromodomains can interact specifically with acetylated lysine, making them the first known protein modules to do so. The nature of the recognition of acetyl-lysine by the P/CAF bromodomain is similar to that of acetyl-CoA by histone acetyltransferase. Thus, the bromodomain is functionally linked to the HAT activity of co-activators in the regulation of gene transcription.

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