THE DR1 DRAP1 HETERODIMER IS A GLOBAL REPRESSOR OF TRANSCRIPTION IN-VIVO/

A general repressor extensively studied in vitro is the human Dr1/DRAP 1 heterodimeric complex. To elucidate the function of Dr1 and DRAP1 in vivo, the yeast Saccharomyces cerevisiae Dr1/DRAP1 repressor complex was identified. The repressor complex is encoded by two essential gene s, designated YDR1 and BUR6. The inviability associated with deletion of the yeast genes can be overcome by expressing the human genes. Howe ver, the human corepressor DRAP1 functions in yeast only when human Dr 1 is coexpressed. The yDr1/Bur6 complex represses transcription in vit ro in a reconstituted RNA polymerase II transcription system. Repressi on of transcription could be overcome by increasing the concentration of TATA-element binding protein (TBP). Consistent with the in vitro re sults, overexpression of YDR1 in vivo resulted in decreased mRNA accum ulation. Furthermore, YDR1 overexpression impaired cell growth, an eff ect that could be rescued by overexpression of TBP. In agreement with our previous studies in vitro, we found that overexpression of Dr1 in vivo also affected the accumulation of RNA polymerase III transcripts, but not of RNA polymerase I transcripts. Our results demonstrate that Dr1functions as a repressor of transcription in vivo and, moreover, d irectly targets TBP, a global regulator of transcription.