Jia Songtao, Noma Ken-ichi, Grewal Shiv I S
Laboratory of Molecular Cell Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Science. 2004 Jun 25;304(5679):1971-6. doi: 10.1126/science.1099035.
At the silent mating-type interval of fission yeast, the RNA interference (RNAi) machinery cooperates with cenH, a DNA element homologous to centromeric repeats, to initiate heterochromatin formation. However, in RNAi mutants, heterochromatin assembly can still occur at low efficiency. Here, we report that Atf1 and Pcr1, two ATF/CREB family proteins, act in a parallel mechanism to the RNAi pathway for heterochromatin nucleation. Deletion of atf1 or pcr1 alone has little effect on silencing at the mating-type region, but when combined with RNAi mutants, double mutants fail to nucleate heterochromatin assembly. Moreover, deletion of atf1 or pcr1 in combination with cenH deletion causes loss of silencing and heterochromatin formation. Furthermore, Atf1 and Pcr1 bind to the mating-type region and target histone H3 lysine-9 methylation and the Swi6 protein essential for heterochromatin assembly. These analyses link ATF/CREB family proteins, involved in cellular response to environmental stresses, to nucleation of constitutive heterochromatin.
在裂殖酵母的沉默交配型间隔期，RNA干扰（RNAi）机制与cenH（一种与着丝粒重复序列同源的DNA元件）协作，启动异染色质形成。然而，在RNAi突变体中，异染色质组装仍可低效发生。在此，我们报告Atf1和Pcr1这两种ATF/CREB家族蛋白，在异染色质成核过程中以与RNAi途径平行的机制发挥作用。单独缺失atf1或pcr1对交配型区域的沉默影响不大，但与RNAi突变体结合时，双突变体无法启动异染色质组装。此外，atf1或pcr1缺失与cenH缺失相结合会导致沉默和异染色质形成的丧失。此外，Atf1和Pcr1结合到交配型区域，并靶向组蛋白H3赖氨酸-9甲基化以及异染色质组装所必需的Swi6蛋白。这些分析将参与细胞对环境应激反应的ATF/CREB家族蛋白与组成型异染色质的成核联系起来。
