In mammalian cells, transcription is regulated in part by high molecular weight coactivating complexes that mediate signals between transcriptional activators and RNA polymerase. These complexes include CRSP (for cofactor required for Sp1 activation), which is required, in conjunction with TAFIIs, for transcriptional activation by Sp1. CRSP is ubiquitously expressed in various tissues and functions as a multimeric complex that consists of nine distinct subunits. Several members of the CRSP family share sequence similarity with multiple components of the yeast transcriptional mediator proteins, including CRSP150, which is related to yeast Rgr1, and CRSP70, which is similar to the elongation factor TFIIS. CRSP77 and CRSP150 are also related to proteins within the putative murine mediator complex, while CRSP130 and CRSP34 are largely unrelated to either murine or yeast proteins. CRSP subunits also associate with larger multimeric coactivaor complexes, including ARC/DRI, which binds directly to SREBP and nuclear hormone receptors to facilitate transcription, and with NAT, a polymerase II-interacting complex that represses activated transcription.