Hengartner C J, Myer V E, Liao S M, Wilson C J, Koh S S, Young R A
Whitehead Institute for Biomedical Research, Cambridge, Massachusetts 02142, USA.
Mol Cell. 1998 Jul;2(1):43-53. doi: 10.1016/s1097-2765(00)80112-4.
Two cyclin-dependent kinases have been identified in yeast and mammalian RNA polymerase II transcription initiation complexes. We find that the two yeast kinases are indistinguishable in their ability to phosphorylate the RNA polymerase II CTD, and yet in living cells one kinase is a positive regulator and the other a negative regulator. This paradox is resolved by the observation that the negative regulator, Srb10, is uniquely capable of phosphorylating the CTD prior to formation of the initiation complex on promoter DNA, with consequent inhibition of transcription. In contrast, the TFIIH kinase phosphorylates the CTD only after the transcription apparatus is associated with promoter DNA. These results reveal that the timing of CTD phosphorylation can account for the positive and negative functions of the two kinases and provide a model for Srb10-dependent repression of genes involved in cell type specificity, meiosis, and sugar utilization.
在酵母和哺乳动物RNA聚合酶II转录起始复合物中已鉴定出两种细胞周期蛋白依赖性激酶。我们发现，这两种酵母激酶在磷酸化RNA聚合酶II CTD的能力上并无差异，但在活细胞中，一种激酶是正调控因子，另一种是负调控因子。通过观察发现负调控因子Srb10在启动子DNA上起始复合物形成之前能够独特地磷酸化CTD，从而抑制转录，这一矛盾得以解决。相比之下，TFIIH激酶仅在转录装置与启动子DNA结合后才磷酸化CTD。这些结果表明，CTD磷酸化的时机可以解释这两种激酶的正负功能，并为Srb10依赖的参与细胞类型特异性、减数分裂和糖利用的基因抑制提供了一个模型。
