Cellular functions of the transposon-derived domesticated SETMAR gene in human cells

转座子是利用宿主细胞的资源自我繁殖的分子寄生虫。尽管转座因子具有寄生性，但越来越多的证据表明，转座因子在基因进化中是一股强大的力量。例如，转座子序列可以成为宿主基因的一部分，然后为宿主履行功能。然而，这些“驯化的”转座子衍生基因的细胞功能在很大程度上是未知的。一个转座酶编码区融合到一个组蛋白甲基转移酶基因约5000万年前在一个共同的祖先的灵长类动物。这种称为SETMAR的嵌合基因在整个人体内表达，并且正选择一直在所有的哺乳动物谱系中保留其编码序列。SETMAR在体外表现出组蛋白甲基转移酶以及转座子DNA结合和切口活性。SETMAR的生理功能仍然是一个谜。我们提出假设驱动的研究，假定SETMAR蛋白和它的1500个结合位点分散在人类基因组构成了灵长类动物特异性基因调控网络。我们考虑两个主要的研究路线，通过基因座特异性染色质修饰和/或通过调节转座子衍生的人类microRNA的功能，解决SETMAR在基因调控中的作用。这项研究将有助于深入了解转座因子在人类进化中的作用和机制。

Transposons are molecular parasites that propagate themselves using resources of the host cell. Despite their parasitic nature, there is increasing evidence that transposable elements are a powerful force in gene evolution. For example, transposon sequences can become parts of host genes, and thereafter fulfill functions for the host. However, the cellular functions of these “domesticated”, transposon-derived genes are largely unknown. A transposase coding region got fused to a histone methyltransferase gene ~50 million years ago in a common ancestor of anthropoid primates. This chimeric gene, called SETMAR, is expressed throughout the human body, and positive selection has been preserving its coding sequence in all anthropoid lineages. SETMAR exhibits histone methyltransferase as well as transposon DNA binding and nicking activities in vitro. The physiological function of SETMAR remains an enigma. We propose hypothesis-driven research that presumes that the SETMAR protein and its ≈1500 binding sites dispersed in the human genome constitute a primate-specific gene regulatory network. We consider two major lines of research addressing a role of SETMAR in gene regulation through locus-specific chromatin modifications and/or by regulating the function of transposon-derived human microRNAs. The proposed research could provide insights into the mechanisms and roles of transposable elements in human evolution.