RNAi-independent heterochromatin nucleation by the stress-activated ATF/CREB family proteins
RNAi-independent heterochromatin nucleation by the stress-activated ATF/CREB family proteins
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DOI：
10.1126/science.1099035
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发表时间：
2004-06-25
期刊：
影响因子：
56.9
通讯作者：
Grewal, SIS
中科院分区：
文献类型：
--
作者：
Jia, ST;Noma, K;Grewal, SIS
在分裂酵母的沉默交配型间隔中，RNA干扰（RNAi）机制与cenH（一种与着丝粒重复序列同源的DNA元件）合作，以启动异染色质形成。然而，在RNAi突变体中，异染色质组装仍然可以以低效率发生。在这里，我们报告Atf 1和Pcr 1，两个ATF/CREB家族蛋白，在一个平行的机制，以RNAi途径异染色质成核。单独缺失atf 1或pcr 1对交配型区域的沉默几乎没有影响，但是当与RNAi突变体组合时，双突变体不能使异染色质组装成核。此外，atfl或pcrl的缺失与cenH缺失的组合导致沉默的丧失和异染色质形成。此外，Atf 1和Pcr 1结合到交配型区域，并靶向组蛋白H3赖氨酸-9甲基化和异染色质组装所必需的Swi 6蛋白。这些分析链接ATF/CREB家族蛋白，参与细胞对环境压力的反应，组成异染色质的成核。
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.