Cang Yong, Prelich Gregory
Department of Molecular Genetics, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461, USA.
Proc Natl Acad Sci U S A. 2002 Oct 1;99(20):12727-32. doi: 10.1073/pnas.202236699. Epub 2002 Sep 17.
Negative cofactor 2 (NC2) is an evolutionarily conserved transcriptional regulator that was originally identified as an inhibitor of basal transcription. Its inhibitory mechanism has been extensively characterized; NC2 binds to the TATA-binding protein (TBP), blocking the recruitment of TFIIA and TFIIB, and thereby inhibiting preinitiation complex assembly. NC2 is also required for expression of many yeast genes in vivo and stimulates TATA-less transcription in a Drosophila in vitro transcription system, but the mechanism responsible for the NC2-mediated stimulation of transcription is not understood. Here we establish that yeast NC2 can directly stimulate activated transcription from TATA-driven promoters both in vivo and in vitro, and moreover that this positive role requires the same surface of TBP that mediates the NC2 repression activity. On the basis of these results, we propose a model to explain how NC2 can mediate both repression and activation through the same surface of TBP.
负辅因子2(NC2)是一种进化上保守的转录调节因子,最初被鉴定为基础转录的抑制剂。其抑制机制已得到广泛研究;NC2与TATA结合蛋白(TBP)结合,阻止TFIIA和TFIIB的募集,从而抑制起始前复合物的组装。在体内,许多酵母基因的表达也需要NC2,并且在果蝇体外转录系统中,NC2能刺激无TATA的转录,但NC2介导转录刺激的机制尚不清楚。在这里,我们证实酵母NC2在体内和体外都能直接刺激由TATA驱动的启动子的激活转录,而且这种正向作用需要TBP的同一表面来介导NC2的抑制活性。基于这些结果,我们提出了一个模型来解释NC2如何通过TBP的同一表面介导抑制和激活作用。