PDF(Pubmed)
Abstract：
Cilia, either motile or non-motile (a.k.a primary or sensory), are complex evolutionarily conserved eukaryotic structures composed of hundreds of proteins required for their assembly, structure and function that are collectively known as the ciliome. Ciliome gene mutations underlie a group of pleiotropic genetic diseases known as ciliopathies. Proper cilium function requires the tight coregulation of ciliome gene transcription, which is only fragmentarily understood. RFX transcription factors (TF) have an evolutionarily conserved role in the direct activation of ciliome genes both in motile and non-motile cilia cell-types. In vertebrates, FoxJ1 and FoxN4 Forkhead (FKH) TFs work with RFX in the direct activation of ciliome genes, exclusively in motile cilia cell-types. No additional TFs have been described to act together with RFX in primary cilia cell-types in any organism. Here we describe FKH-8, a FKH TF, as a direct regulator of the sensory ciliome genes in Caenorhabditis elegans. FKH-8 is expressed in all ciliated neurons in C. elegans, binds the regulatory regions of ciliome genes, regulates ciliome gene expression, cilium morphology and a wide range of behaviors mediated by sensory ciliated neurons. FKH-8 and DAF-19 (C. elegans RFX) physically interact and synergistically regulate ciliome gene expression. C. elegans FKH-8 function can be replaced by mouse FOXJ1 and FOXN4 but not by other members of other mouse FKH subfamilies. In conclusion, RFX and FKH TF families act jointly as direct regulators of ciliome genes also in sensory ciliated cell types suggesting that this regulatory logic could be an ancient trait predating functional cilia sub-specialization.
摘要：
Cilia,运动或非运动(也称为初级或感官)，是复杂的进化保守的真核结构，由数百种组装所需的蛋白质组成，结构和功能统称为Ciliome。Ciliome基因突变是一组称为纤毛病的多效性遗传疾病的基础。正确的纤毛功能需要纤毛基因转录的紧密协同调节，这只是零碎的理解。RFX转录因子（TF）在活动和非活动纤毛细胞类型的纤毛基因的直接激活中具有进化上保守的作用。在脊椎动物中，FoxJ1和FoxN4叉头（FKH）TFs与RFX一起直接激活ciliome基因，仅在能动的纤毛细胞类型中。在任何生物体的原代纤毛细胞类型中，没有其他TF与RFX一起起作用。这里我们描述FKH-8，一种FKHTF，作为秀丽隐杆线虫感觉纤毛基因的直接调节因子。FKH-8在C.elegans的所有纤毛神经元中表达，结合纤微组基因的调节区，调节Ciliome基因表达，纤毛形态和由感觉纤毛神经元介导的广泛行为。FKH-8和DAF-19(C.秀丽隐杆线虫RFX）物理相互作用并协同调节纤丝基因组基因表达。线虫FKH-8功能可以被小鼠FOXJ1和FOXN4取代，但不能被其他小鼠FKH亚家族的其他成员取代。总之,RFX和FKHTF家族在感觉纤毛细胞类型中也共同充当纤毛基因的直接调节剂，这表明这种调节逻辑可能是早于功能性纤毛亚专业化的古老特征。
