In addition to those that are members of the GNAT and MYST families, there are several other proteins found typically in higher eukaryotes that exhibit HAT activity. These include p300/CBP, nuclear receptor coactivators (e.g., ACTR/SRC-1), TAFII250, TFIIIC, Rtt109, and CLOCK. p300/CBP are metazoan-specific and contain several zinc finger regions, a bromodomain, a catalytic (HAT) domain, and regions that interact with other transcription factors. Importantly, the HAT domain shows no sequence homology to other known HATs, and it is required for p300/CBP to function in transcriptional activation. In addition, these proteins contain several HAT domain motifs (A, B, and D) that are similar to those of the GNATs. They also possess a novel motif E that is homologous to sequences in the HAT domains of GNATs. TFIIIC is one of the general transcription factors involved in RNA polymerase III-mediated transcription. Three components in the human protein have been shown to possess independent HAT activity (hTFIIIC220, hTFIIIC110, and hTFIIIC90). Rtt109 is a fungal-specific HAT that requires association with histone chaperone proteins for activity. The HAT activities of the human TAFII250 and CLOCK coactivators have not been studied as extensively. TAFII250 is one of the TBP-associated factor subunits of TFIID, and it shares a Gly-X-Gly pattern with Gcn5 that is important for HAT activity. CLOCK is a circadian rhythm master regulator that functions with BMAL1 to carry out its HAT activity.