Joh Richard I, Khanduja Jasbeer S, Calvo Isabel A, Mistry Meeta, Palmieri Christina M, Savol Andrej J, Ho Sui Shannan J, Sadreyev Ruslan I, Aryee Martin J, Motamedi Mo
Massachusetts General Hospital Center for Cancer Research and Department of Medicine, Harvard Medical School, Charlestown, MA 02129, USA.
Bioinformatics Core, Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA.
Mol Cell. 2016 Dec 15;64(6):1088-1101. doi: 10.1016/j.molcel.2016.11.020.
Quiescence (G0) is a ubiquitous stress response through which cells enter reversible dormancy, acquiring distinct properties including reduced metabolism, resistance to stress, and long life. G0 entry involves dramatic changes to chromatin and transcription of cells, but the mechanisms coordinating these processes remain poorly understood. Using the fission yeast, here, we track G0-associated chromatin and transcriptional changes temporally and show that as cells enter G0, their survival and global gene expression programs become increasingly dependent on Clr4/SUV39H, the sole histone H3 lysine 9 (H3K9) methyltransferase, and RNAi proteins. Notably, G0 entry results in RNAi-dependent H3K9 methylation of several euchromatic pockets, prior to which Argonaute1-associated small RNAs from these regions emerge. Overall, our data reveal another function for constitutive heterochromatin proteins (the establishment of the global G0 transcriptional program) and suggest that stress-induced alterations in Argonaute-associated sRNAs can target the deployment of transcriptional regulatory proteins to specific sequences.
静止期（G0）是一种普遍存在的应激反应，通过这种反应细胞进入可逆性休眠状态，获得包括代谢降低、抗应激能力和长寿等独特特性。进入G0期涉及染色质和细胞转录的显著变化，但协调这些过程的机制仍知之甚少。在此，我们利用裂殖酵母，对与G0相关的染色质和转录变化进行了时间追踪，结果表明，随着细胞进入G0期，它们的存活和全局基因表达程序越来越依赖于Clr4/SUV39H（唯一的组蛋白H3赖氨酸9（H3K9）甲基转移酶）和RNAi蛋白。值得注意的是，进入G0期会导致几个常染色质区域发生RNAi依赖的H3K9甲基化，在此之前，来自这些区域的与AGO1相关的小RNA会出现。总体而言，我们的数据揭示了组成型异染色质蛋白的另一个功能（全局G0转录程序的建立），并表明应激诱导的AGO相关小RNA的改变可以将转录调节蛋白部署到特定序列。
