Ames Amanda, Seman Melissa, Larkin Ajay, Raiymbek Gulzhan, Chen Ziyuan, Levashkevich Alexander, Kim Bo, Biteen Julie Suzanne, Ragunathan Kaushik
bioRxiv. 2024 May 6:2023.11.28.569027. doi: 10.1101/2023.11.28.569027.
HP1 proteins are essential for establishing and maintaining transcriptionally silent heterochromatin. They dimerize, forming a binding interface to recruit diverse chromatin-associated factors. HP1 proteins are specialized and rapidly evolve, but the extent of variation required to achieve functional specialization is unknown. To investigate how changes in amino acid sequence impacts epigenetic inheritance, we performed a targeted mutagenesis screen of the S. pombe HP1 homolog, Swi6. Substitutions within an auxiliary surface adjacent to the HP1 dimerization interface produced Swi6 variants with divergent maintenance properties. Remarkably, substitutions at a single amino acid position led to the persistent gain or loss of epigenetic inheritance. These substitutions increased Swi6 chromatin occupancy in vivo and altered Swi6-protein interactions that reprogram H3K9me maintenance. We show that relatively minor changes in Swi6 amino acid composition can lead to profound changes in epigenetic inheritance which provides a redundant mechanism to evolve novel effector specificity. .
HP1蛋白对于建立和维持转录沉默的异染色质至关重要。它们会二聚化，形成一个结合界面以招募多种与染色质相关的因子。HP1蛋白具有特异性且进化迅速，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表观遗传遗传，我们对粟酒裂殖酵母HP1同源物Swi6进行了靶向诱变筛选。在与HP1二聚化界面相邻的一个辅助表面内的替换产生了具有不同维持特性的Swi6变体。值得注意的是，单个氨基酸位置的替换导致表观遗传遗传的持续获得或丧失。这些替换增加了Swi6在体内的染色质占有率，并改变了重新编程H3K9me维持的Swi6-蛋白质相互作用。我们表明，Swi6氨基酸组成中相对较小的变化可导致表观遗传遗传的深刻变化，这提供了一种进化新效应子特异性的冗余机制。
