Kretzschmar M, Meisterernst M, Roeder R G
Laboratory of Biochemistry and Molecular Biology, Rockefeller University, New York, NY 10021.
Proc Natl Acad Sci U S A. 1993 Dec 15;90(24):11508-12. doi: 10.1073/pnas.90.24.11508.
The transcriptional activation of eukaryotic class II genes by sequence-specific regulatory proteins requires cofactors in addition to the general transcription factors. One cofactor (termed PC3) was purified from HeLa cells and identified by sequence analysis and functional assays as human DNA topoisomerase I (EC5.99.1.2). Under identical conditions PC3 mediates both a net activation of transcription by the acidic activator GAL4-AH and repression of basal transcription, thereby leading to a large induction of transcription by the activator. PC3-mediated activation of transcription is dependent on the presence of both the GAL4-AH activation domain and the TATA-binding protein (TBP)-associated-factors (TAFs) in natural transcription factor TFIID, while repression of basal transcription is observed with either TFIID or the derived TBP alone. These results suggest novel functions, apparently through distinct mechanisms, for human DNA topoisomerase I in the regulation of transcription initiation by RNA polymerase II.
除了通用转录因子外，序列特异性调节蛋白对真核生物II类基因的转录激活还需要辅助因子。一种辅助因子（称为PC3）从HeLa细胞中纯化出来，并通过序列分析和功能测定鉴定为人DNA拓扑异构酶I（EC5.99.1.2）。在相同条件下，PC3既介导酸性激活剂GAL4-AH对转录的净激活，又介导基础转录的抑制，从而导致激活剂对转录的大量诱导。PC3介导的转录激活依赖于天然转录因子TFIID中GAL4-AH激活域和TATA结合蛋白（TBP）相关因子（TAFs）的同时存在，而单独使用TFIID或衍生的TBP时则观察到基础转录的抑制。这些结果表明，人DNA拓扑异构酶I在RNA聚合酶II转录起始调控中具有新的功能，显然是通过不同的机制实现的。
