In eukaryotes, the Suv39 family of proteins tri-methylate lysine 9 of histone H3 (H3K9me) to form constitutive heterochromatin. However, how Suv39 proteins are nucleated at heterochromatin is not fully described. In the fission yeast, current models posit that Argonaute1-associated small RNAs (sRNAs) nucleate the sole H3K9 methyltransferase, Clr4/SUV39H, to centromeres. Here, we show that in the absence of all sRNAs and H3K9me, the Mtl1 and Red1 core (MTREC)/PAXT complex nucleates Clr4/SUV39H at a heterochromatic long noncoding RNA (lncRNA) at which the two H3K9 deacetylases, Sir2 and Clr3, also accumulate by distinct mechanisms. Iterative cycles of H3K9 deacetylation and methylation spread Clr4/SUV39H from the nucleation center in an sRNA-independent manner, generating a basal H3K9me state. This is acted upon by the RNAi machinery to augment and amplify the Clr4/H3K9me signal at centromeres to establish heterochromatin. Overall, our data reveal that lncRNAs and RNA quality control factors can nucleate heterochromatin and function as epigenetic silencers in eukaryotes.

在真核生物中，Suv39 蛋白家族将组蛋白 H3 (H3K9me) 的赖氨酸 9 三甲基化，形成组成型异染色质。然而，Suv39 蛋白如何在异染色质处成核尚未完全描述。在裂殖酵母中，当前模型假设 Argonaute1 相关小 RNA (sRNA) 将唯一的 H3K9 甲基转移酶 Clr4/SUV39H 成核至着丝粒。在这里，我们表明，在所有 sRNA 和 H3K9me 都不存在的情况下，Mtl1 和 Red1 核心 (MTREC)/PAXT 复合物在异染色长非编码 RNA (lncRNA) 处使 Clr4/SUV39H 成核，其中两个 H3K9 脱乙酰酶 Sir2 和 Clr3 也通过不同的机制积累。 H3K9 脱乙酰化和甲基化的迭代循环以不依赖 sRNA 的方式从成核中心扩散 Clr4/SUV39H，产生基础 H3K9me 状态。 RNAi 机制对此起作用，增强和放大着丝粒处的 Clr4/H3K9me 信号，从而建立异染色质。总体而言，我们的数据表明，lncRNA 和 RNA 质量控制因子可以使异染色质成核，并在真核生物中充当表观遗传沉默子。