Structure and ligand of a histone acetyltransferase bromodomain.
Article Details
- CitationCopy to clipboard
Dhalluin C, Carlson JE, Zeng L, He C, Aggarwal AK, Zhou MM
Structure and ligand of a histone acetyltransferase bromodomain.
Nature. 1999 Jun 3;399(6735):491-6.
- PubMed ID
- 10365964 [ View in PubMed]
- Abstract
Histone acetylation is important in chromatin remodelling and gene activation. Nearly all known histone-acetyltransferase (HAT)-associated transcriptional co-activators contain bromodomains, which are approximately 110-amino-acid modules found in many chromatin-associated proteins. 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). 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.