PDF(Pubmed)
Abstract：
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 the S. pombe HP1 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.
摘要：
HP1蛋白对于建立和维持转录沉默异染色质至关重要。他们二聚化，形成一个结合界面来招募不同的染色质相关因子。尽管已知HP1蛋白快速进化，实现功能专业化所需的变异程度是未知的。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.pombeHP1同源物进行了靶向诱变筛选，Swi6.与HP1二聚化界面相邻的辅助表面内的替换产生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-蛋白质相互作用，从而重新编程了H3K9me的维持。我们展示了辅助表面中Swi6氨基酸组成的相对较小的变化如何导致表观遗传遗传的深刻变化，从而提供了进化HP1效应子特异性的冗余机制。
