Evolutionary plasticity in the innate immune function of Akirin

Eukaryotic gene expression requires the coordinated action of transcription factors, chromatin remodelling complexes and RNA polymerase. The conserved nuclear protein Akirin plays a central role in immune gene expression in insects and mammals, linking the SWI/SNF chromatin-remodelling complex with the transcription factor NFκB. Although nematodes lack NFκB, Akirin is also indispensable for the expression of defence genes in the epidermis of Caenorhabditis elegans following natural fungal infection. Through a combination of reverse genetics and biochemistry, we discovered that in C. elegans Akirin has conserved its role of bridging chromatin-remodellers and transcription factors, but that the identity of its functional partners is different since it forms a physical complex with NuRD proteins and the POU-class transcription factor CEH-18. In addition to providing a substantial step forward in our understanding of innate immune gene regulation in C. elegans, our results give insight into the molecular evolution of lineage-specific signalling pathways.

真核基因表达需要转录因子、染色质重塑复合物与RNA聚合酶的协同作用。保守核蛋白Akirin在昆虫和哺乳动物的免疫基因表达中发挥核心作用，可将SWI/SNF染色质重塑复合物与转录因子NFκB连接起来。尽管线虫缺少NFκB，但在自然真菌感染后，秀丽隐杆线虫（Caenorhabditis elegans）表皮的防御基因表达也离不开Akirin。本研究通过反向遗传学与生物化学相结合的手段，发现秀丽隐杆线虫中的Akirin仍保留了作为染色质重塑因子与转录因子之间桥梁的功能，但其功能伙伴的种类有所不同：它可与NuRD蛋白以及POU家族转录因子CEH-18形成物理复合物。本研究结果不仅大幅推进了我们对秀丽隐杆线虫先天免疫基因调控机制的理解，还为谱系特异性信号通路的分子进化研究提供了新的见解。