Proteolytic and scanning electron microscopy studies indicate that S. cerevisiae TFIIIC consists of two globular domains separated by a flexible linker, one of which, designated tau B, binds strongly to the B box, and the other, designated tau A, binds weakly to the A box, of type 2 promoters (Marzouki et al., 1986). DNA footprinting and protein-protein interaction studies (Hsieh et al., 1999; Hsieh et al., 1999; Kovelman and Roeder, 1992; Shen et al., 1996; Yoshinaga et al., 1989) support the models shown in the figure. The components of Brf1-TFIIIB (see TFIIIB entries) are shown in grey, and TFIIIA is shown in blue. Sites of strong protein-DNA cross-linking are indicated by small ovals. Black and grey rectangles show protein-protein contacts observed in human and S. cerevisiae TFIIIC subunits, respectively. The general arrangement of the TFIIIC subunits on type 1 and 2 promoters is strikingly similar (Bartholomew et al., 1990; Braun et al., 1992a).

On a type 2 promoter, the S. cerevisiae Tfc3 subunit cross-links primarily just upstream of the B box and Tfc6 cross-links at the end of the gene (Bartholomew et al., 1990). Tfc1 and Tfc7 have strong cross-links within and near the 3 end of the A box, respectively (Bartholomew et al., 1990). Tfc8 does not cross-link to DNA, and after partial protease digestion of TFIIIC, is found in the tB domain. In addition, however, Tfc8 displays genetic interactions with Tfc1, TBP, and ScBdp1, and it associates with TBP in vitro, suggesting that it is also present in the tA domain. The Tfc4 subunit cross-links to sites around and upstream of the transcription start site (Bartholomew et al., 1990) and directly contacts both the ScBrf1 and ScBdp1 subunits of TFIIIB.

Numerous protein-protein contacts between various TFIIIC subunits have been described, which are symbolized by small rectangles in the figure. The black rectangles indicate contacts identified with human TFIIIC subunits, the grey rectangles with S. cerevisiae TFIIIC subunits. Thus, Tfc7 interacts directly with Tfc1. TTFIIIC90 interacts with TFIIIC220, TFIIIC110, and TFIIIC63 (Hsieh et al., 1999). TFIIIC102 interacts with TFIIIC63 (Hsieh et al., 1999). Various TFIIIC subunits also interact directly with Brf1-TFIIIB subunits, as shown in the figure.