Identification of a novel, tunable interface in the S.pombe HP1 protein, Swi6, that underpins epigenetic inheritance.
Identification of a novel, tunable interface in the S.pombe HP1 protein, Swi6, that underpins epigenetic inheritance.
复制标题
鉴定了粟酒裂殖酵母 HP1 蛋白 Swi6 中的一个新型可调节界面，该界面支持表观遗传。
DOI：
10.1101/2023.11.28.569027
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发表时间：
2023
期刊：
影响因子：
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通讯作者：
Ragunathan,Kaushik
中科院分区：
文献类型：
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作者：
Ames,Amanda;Seman,Melissa;Larkin,Ajay;Raiymbek,Gulzhan;Chen,Ziyuan;Levashkevich,Alex;Biteen,JulieSuzanne;Ragunathan,Kaushik
HP1蛋白对于建立和维持转录沉默的异染色质是必不可少的。它们二聚化，形成结合界面以募集不同的染色质相关因子。虽然已知HP1蛋白快速进化，但实现功能特化所需的变异程度尚不清楚。为了研究氨基酸序列的变化如何影响异染色质的形成，我们对S。pombeHP 1同源物，Swi6.在邻近HP1二聚化界面的辅助表面内的取代产生具有不同维持性质的Swi6变体。值得注意的是，在单个氨基酸位置的取代导致表观遗传的持续获得或丧失。这些取代增加了Swi6染色质在体内的占有率，并改变了Swi6蛋白的相互作用，重新编程H3K9me的维护。我们展示了Swi6氨基酸组成在辅助表面中的相对微小的变化如何导致表观遗传的深刻变化，从而提供了一种冗余的机制来进化HP1效应子特异性。
HP1 proteins are essential for establishing and maintaining transcriptionally silent heterochromatin. They dimerize, forming a binding interface to recruit diverse chromatin-associated factors. Although HP1 proteins are known to rapidly evolve, the extent of variation required to achieve functional specialization is unknown. To investigate how changes in amino acid sequence impacts heterochromatin formation, we performed a targeted mutagenesis screen of theS. pombeHP1 homolog, Swi6. Substitutions within an auxiliary surface adjacent to the HP1 dimerization interface produce Swi6 variants with divergent maintenance properties. Remarkably, substitutions at a single amino acid position lead to the persistent gain or loss of epigenetic inheritance. These substitutions increase Swi6 chromatin occupancy in vivo and altered Swi6-protein interactions that reprogram H3K9me maintenance. We show how relatively minor changes in Swi6 amino acid composition in an auxiliary surface can lead to profound changes in epigenetic inheritance providing a redundant mechanism to evolve HP1-effector specificity.