Activation of gene transcription in metazoans is a multistep process that is 
triggered by factors that recognize transcriptional enhancer sites in DNA. These 
factors work with co-activators to direct transcriptional initiation by the RNA 
polymerase II apparatus. One class of co-activator, the TAF(II) subunits of 
transcription factor TFIID, can serve as targets of activators and as proteins 
that recognize core promoter sequences necessary for transcription initiation. 
Transcriptional activation by enhancer-binding factors such as Sp1 requires 
TFIID, but the identity of other necessary cofactors has remained unknown. Here 
we describe a new human factor, CRSP, that is required together with the 
TAF(II)s for transcriptional activation by Sp1. Purification of CRSP identifies 
a complex of approximate relative molecular mass 700,000 (M(r) approximately 
700K) that contains nine subunits with M(r) values ranging from 33K to 200K. 
Cloning of genes encoding CRSP subunits reveals that CRSP33 is a homologue of 
the yeast mediator subunit Med7, whereas CRSP150 contains a domain conserved in 
yeast mediator subunit Rgr1. CRSP p200 is identical to the nuclear 
hormone-receptor co-activator subunit TRIP2/PBP. CRSPs 34, 77 and 130 are new 
proteins, but the amino terminus of CRSP70 is homologous to elongation factor 
TFIIS. Immunodepletion studies confirm that these subunits have an essential 
cofactor function. The presence of common subunits in distinct cofactor 
complexes suggests a combinatorial mechanism of co-activator assembly during 
transcriptional activation.