Telomeres, highly ordered DNA-protein complexes at eukaryotic linear chromosome ends, are specialized heterochromatin loci conserved among eukaryotes. In Schizosaccharomyces pombe, the shelterin complex is important for subtelomeric heterochromatin establishment. Despite shelterin has been demonstrated to mediate the recruitment of the Snf2/histone deacetylase-containing repressor complex (SHREC) and the Clr4 methyltransferase complex (CLRC) to telomeres, the mechanism involved in telomeric heterochromatin assembly remains elusive due to the multiple functions of the shelterin complex. Here, we found that CLRC plays a dominant role in heterochromatin establishment at telomeres. In addition, we identified a series of amino acids in the shelterin subunit Ccq1 that are important for the specific interaction between Ccq1 and the CLRC subunit Raf2. Finally, we demonstrated that the Ccq1-Raf2 interaction is essential for the recruitment of CLRC to telomeres, that contributes to histone H3 lysine 9 methylation, nucleosome stability and the shelterin-chromatin association, promoting a positive feedback mechanism for the nucleation and spreading of heterochromatin at subtelomeres. Together, our findings provide a mechanistic understanding of subtelomeric heterochromatin assembly by shelterin-dependent CLRC recruitment to chromosomal ends.

中文翻译：

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Ccq1-Raf2 相互作用介导 CLRC 募集以在端粒建立异染色质。

端粒是真核生物线性染色体末端高度有序的 DNA-蛋白质复合物，是真核生物中保守的特化异染色质基因座。在粟酒裂殖酵母中，shelterin 复合物对于亚端粒异染色质的建立很重要。尽管shellowin已被证明可介导含Snf2/组蛋白去乙酰化酶的阻遏物复合物（SHREC）和Clr4甲基转移酶复合物（CLRC）向端粒的募集，但由于shelterin的多种功能，参与端粒异染色质组装的机制仍然难以捉摸复杂的。在这里，我们发现 CLRC 在端粒的异染色质建立中起主导作用。此外，我们在shelterin 亚基Ccq1 中鉴定了一系列氨基酸，这些氨基酸对于Ccq1 和CLRC 亚基Raf2 之间的特异性相互作用很重要。最后，我们证明了 Ccq1-Raf2 相互作用对于将 CLRC 募集到端粒至关重要，这有助于组蛋白 H3 赖氨酸 9 甲基化，核小体稳定性和shelterin-染色质结合，促进了异染色质在亚端粒的成核和扩散的正反馈机制。总之，我们的研究结果提供了一种机械理解，即通过将遮蔽蛋白依赖的 CLRC 募集到染色体末端来组装亚端粒异染色质。