Canonically, heterochromatin formation in fission yeast and metazoans involves di/trimethylation of histone H3 at lysine 9 position (me2/me3-K9-H3) by the histone methyltransferase (HMT) Suv39/Clr4, followed by binding of Swi6/HP1 to me2/me3-K9-H3 via its chromodomain. Subsequent self-association of Swi6/HP1 on adjacent nucleosomes leads to folded heterochromatin structure. An alternate model suggests a cooperative interaction between Clr4 and Swi6/HP1 in heterochromatin assembly. HP1 binding to RNA has also been invoked for heterochromatin silencing in metazoans. Recruitment of Swi6/HP1 to centromere has been shown to be dependent on the RNAi pathway in fission yeast. Here we show that Swi6/HP1 exhibits a hierarchy of binding affinity to RNAs, ranging from promiscuous, low-affinity binding to mRNAs, to moderate-affinity binding to the RNAi-generated siRNAs corresponding to the dg-dh repeats present in pericentromeric heterochromatin regions, to high-affinity binding to the RNA-DNA hybrids to the cognate dg-dh repeats. Together with the sensitivity of Swi6 localization and silencing to RNaseH, our results suggest a dynamic control of localization of Swi6/HP1 towards the dg-dh repeats versus euchromatic regions. This is mediated by its binding to RNA-DNA hybrid at the dg-dh repeats, as an RNAi-dependent and Me2/me3-K9-H3-independent mechanism of recruitment, leading to heterochromatin formation and silencing.

中文翻译：

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Swi6 / HP1与RNA-DNA杂合体的结合在裂变酵母中着丝粒dg-dh重复序列处启动异染色质组装

典型地，裂变酵母和后生动物中异染色质的形成涉及组蛋白甲基转移酶（HMT）Suv39 / Clr4在赖氨酸9位（me2 / me3-K9-H3）处组蛋白H3的二/三甲基化，然后将Swi6 / HP1与me2 /结合me3-K9-H3通过其色域。Swi6 / HP1随后在相邻核小体上的自缔合导致折叠的异染色质结构。另一个模型表明异染色质组装中Clr4和Swi6 / HP1之间的协同相互作用。HP1与RNA的结合也被用于后生动物的异染色质沉默。Swi6 / HP1向着丝粒的募集已显示取决于裂变酵母中的RNAi途径。在这里，我们显示Swi6 / HP1展现出对RNA的结合亲和力的层次结构，范围从混杂，低亲和力与mRNA结合，dg-dh重复序列存在于着丝粒异质染色质区域，与亲和的dg-dh重复序列的RNA-DNA杂种具有高亲和力。连同Swi6定位和对RNaseH沉默的敏感性，我们的结果表明，动态控制Swi6 / HP1定位于dg-dh重复序列与常染色体区域。这是由于它与dg-dh重复序列上的RNA-DNA杂合体结合而介导的，这是RNAi依赖性和Me2 / me3-K9-H3独立的募集机制，导致异染色质形成和沉默。