TRIP-Brs are a recently discovered set of proteins whose functions remain poorly characterized. Here we report the identification of TRIP-Br3 as a member of the TRIP-Br family along with evidence showing that TRIP-Brs interact with bromodomain-containing transcriptional cofactors PCAF, STAF65γ, and KAP1. PCAF, a histone acetyltransferase; STAF65γ, a protein associated with histone acetylation activity; and KAP1, a corepressor, influence the transcriptional activity of TRIP-Brs differentially. Finally, while all three TRIP-Brs are localized to the nucleus, TRIP-Br2 and TRIP-Br3 are also present in the cytoplasm through interaction with CRM1. Our results suggest that different TRIP-Brs function by interacting with a wide variety of bromodomain-containing transcriptional regulators in different subcellular locales.