Goppelt A, Stelzer G, Lottspeich F, Meisterernst M
Laboratorium für Molekulare Biologie-Genzentrum der Ludwig-Maximilians-Universität München, Germany.
EMBO J. 1996 Jun 17;15(12):3105-16.
Negative co-factor 2 (NC2) regulates transcription of the class II genes through binding to TFIID and inhibition of pre-initiation complex formation. We have isolated and cloned NC2, and investigated the molecular mechanism underlying repression of transcription. NC2 consists of two subunits, termed NC2alpha and NC2beta, the latter of which is identical to Dr1. The NC2 subunits dimerize and bind to TATA binding protein (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 probably contribute to transcriptional repression. Binding of NC2 inhibits association of TFIIB with TBP-promoter complexes. NC2 binds directly to DNA, and binding of NC2 to TBP-promoter complexes affects the conformation of DNA, which could be one cause for the inhibition of TFIIB. In addition, multimerization of repressor-TBP complexes on DNA might inhibit the assembly of the pre-initiation complex. We suggest that binding of the repressor to TRP-promoter complexes establishes a mechanism that controls the rate of transcription by RNA polymerase II.
负辅因子2（NC2）通过与TFIID结合并抑制起始前复合物的形成来调节II类基因的转录。我们已经分离并克隆了NC2，并研究了转录抑制的分子机制。NC2由两个亚基组成，称为NC2α和NC2β，后者与Dr1相同。NC2亚基二聚化并通过H2A-H2B类型的组蛋白折叠结构域与TATA结合蛋白（TBP）-启动子复合物结合。基础转录的抑制需要NC2亚基的组蛋白折叠和羧基末端结构域。几种机制可能有助于转录抑制。NC2的结合抑制TFIIB与TBP-启动子复合物的结合。NC2直接与DNA结合，并且NC2与TBP-启动子复合物的结合会影响DNA的构象，这可能是抑制TFIIB的一个原因。此外，阻遏物-TBP复合物在DNA上的多聚化可能会抑制起始前复合物的组装。我们认为阻遏物与TRP-启动子复合物的结合建立了一种机制，该机制通过RNA聚合酶II控制转录速率。
