A MECHANISM FOR REPRESSION OF CLASS-II GENE-TRANSCRIPTION THROUGH SPECIFIC BINDING OF NC2 TO TBP-PROMOTER COMPLEXES VIA HETERODIMERIC HISTONE FOLD DOMAINS

Negative co-factor 2 (NC2) regulates transcription of the class II gen es through binding to TFIID and inhibition of pre-initiation complex f ormation. We have isolated and cloned NC2, and investigated the molecu lar mechanism underlying repression of transcription. NC2 consists of two subunits, termed NC2 alpha and NC2 beta, the latter of which is id entical to Dr1. The NC2 subunits dimerize and bind to TATA binding pro tein (TBP)-promoter complexes via histone fold domains of the H2A-H2B type, Repression of basal transcription requires the histone fold and carboxy-terminal domains of the NC2 subunits, Several mechanisms proba bly contribute to transcriptional repression. Binding of NC2 inhibits association of TFIIB with TBP-promoter complexes, NC2 binds directly t o DNA, and binding of NC2 to TBP-promoter complexes affects the confor mation of DNA, which could be one cause for the inhibition of TFIIB. I n addition, multimerization of repressor-TBP complexes on DNA might in hibit the assembly of the pre-initiation complex, We suggest that bind ing of the repressor to TBP-promoter complexes establishes a mechanism that controls the rate of transcription by RNA polymerase II.