Oficjalska-Pham Danuta, Harismendy Olivier, Smagowicz Wieslaw J, Gonzalez de Peredo Anne, Boguta Magdalena, Sentenac André, Lefebvre Olivier
Laboratoire de Transcription des Gènes, Service de Biochimie et Génétique Moléculaire, CEA/Saclay, 91191 Gif-sur-Yvette Cedex, France.
Mol Cell. 2006 Jun 9;22(5):623-32. doi: 10.1016/j.molcel.2006.04.008.
We report genome-wide analyses that establish Maf1 as a general and direct repressor of yeast RNA polymerase (Pol) III transcription. Chromatin immunoprecipitation (ChIP) coupled to microarray hybridization experiments showed an increased association of Maf1 to Pol III-transcribed genes under repressing condition (rapamycin treatment) correlated with a dissociation of Brf1 and Pol III. Maf1 can exist in various phosphorylation states and interacts with Pol III in a dephosphorylated state. The largest subunit of Pol III, C160, was identified as a target of Maf1. Under repressing conditions, Maf1 is dephosphorylated and accumulates in the nucleus, and Pol III-Maf1 interaction increases. Mutations in protein phosphatase type 2A (PP2A) catalytic subunit-encoding genes prevented rapamycin-induced Maf1 dephosphorylation, its nuclear accumulation, and repression of Pol III transcription. The results indicate that Pol III transcription can be globally and rapidly downregulated via dephosphorylation and relocation of a general negative cofactor.
我们报告了全基因组分析，该分析确定Maf1是酵母RNA聚合酶（Pol）III转录的一种普遍且直接的抑制因子。染色质免疫沉淀（ChIP）与微阵列杂交实验相结合表明，在抑制条件下（雷帕霉素处理），Maf1与Pol III转录基因的结合增加，这与Brf1和Pol III的解离相关。Maf1可以以多种磷酸化状态存在，并在去磷酸化状态下与Pol III相互作用。Pol III的最大亚基C160被确定为Maf1的一个靶点。在抑制条件下，Maf1去磷酸化并在细胞核中积累，并且Pol III-Maf1相互作用增加。蛋白磷酸酶2A（PP2A）催化亚基编码基因的突变阻止了雷帕霉素诱导的Maf1去磷酸化、其核积累以及Pol III转录的抑制。结果表明，Pol III转录可以通过一种普遍的负性辅因子的去磷酸化和重新定位而被全局且快速地下调。
