TFIID is a large multiprotein complex that initiates assembly of the 
transcription machinery. It is unclear how TFIID recognizes promoters in vivo 
when templates are nucleosome-bound. Here, it is shown that TAFII250, the 
largest subunit of TFIID, contains two tandem bromodomain modules that bind 
selectively to multiply acetylated histone H4 peptides. The 2.1 angstrom crystal 
structure of the double bromodomain reveals two side-by-side, four-helix bundles 
with a highly polarized surface charge distribution. Each bundle contains an 
Nepsilon-acetyllysine binding pocket at its center, which results in a structure 
ideally suited for recognition of diacetylated histone H4 tails. Thus, TFIID may 
be targeted to specific chromatin-bound promoters and may play a role in 
chromatin recognition.