The transcriptional cofactor complex CRSP is required for activity of the enhancer-binding protein Sp1

Activation of gene transcription in metazoans is a multistep process that i s triggered by factors that recognize transcriptional enhancer sites in DNA , These factors work with co-activators to direct transcriptional initiatio n by the RNA polymerase II apparatus(1), One class of co-activator, the TAF (II) subunits of transcription factor TFIID, can serve as targets of activa tors and as proteins that recognize core promoter sequences necessary for t ranscription initiation(2-5). Transcriptional activation by enhancer-bindin g factors such as Sp1 (ref, 6) requires TFIID, but the identity of other ne cessary cofactors has remained unknown. Here we describe a new human factor , CRSP, that is required together with the TAF(II)s for transcriptional act ivation by Sp1. Purification of CRSP identifies a complex of approximate re lative molecular mass 700,000 (M(r)similar to 700K) that contains nine subu nits with M-r values ranging from 33K to 200K. Cloning of genes encoding CR SP subunits reveals that CRSP33 is a homologue of the yeast mediator subuni t Med7 (ref. 7), whereas CRSP150 contains a domain conserved in yeast media tor subunit Rgr1 (ref. 8), CRSP p200 is identical to the nuclear hormone-re ceptor co-activator subunit TRIP2/PBP9,10. CRSPs 34, 77 and 130 are new pro teins, but the amino terminus of CRSP70 is homologous to elongation factor TFIIS11. Immunodepletion studies confirm that these subunits have an essent ial cofactor function. The presence of common subunits in distinct cofactor complexes suggests a combinatorial mechanism of co-activator assembly duri ng transcriptional activation.