BAZ-2和SET-6通过BLMP-1调控秀丽隐杆线虫衰老

BAZ-2 and SET-6 Modulate Aging via BLMP-1 in C.elegans

该文使用秀丽隐杆线虫作为模式动物,探讨了两个表观遗传因子BAZ-2和SET-6通过BLMP-1调控编码线粒体功能蛋白核基因的表达,进而调控线虫衰老。利用JASPAR数据库,分析了baz-2和set-6突变体线虫中表达上调基因的启动子区域DNA序列,发现转录因子BLMP-1的特征结合位点在这些序列中富集。随后分别在baz-2和set-6突变体线虫中敲除blmp-1基因,检测blmp1;baz-2和blmp-1;set-6双敲除突变体线虫的寿命、咽喉肌肉跳动能力、基础型和增强型食物诱导的缓慢运动反应、抗氧化应激能力和线粒体功能相关基因的表达水平,发现敲除blmp-1消除了baz-2和set-6突变体线虫寿命较长,咽喉肌肉跳动、基础型和增强型食物诱导的缓慢运动反应和抗氧化能力较好的行为表型,以及线粒体功能相关基因表达上调的现象。该研究阐明了BAZ-2和SET-6通过BLMP-1调控线虫衰老的机制。

This study aims to explore whether two epigenetic regulators,BAZ-2 and SET-6,modulate aging via BLMP-1 by regulating the expression of nuclear genes encoding mitochondrial protein in C.elegans(Caenorhabditis elegans).Through data analysis in JASPAR database,the binding site of the transcription factor BLMP-1 was found to be enriched in the sequence of promoter region of up-regulated expression genes found in both baz-2 and set-6 mutant worms.By knocking out blmp-1 in baz-2 and set-6 mutant worms respectively,blmp-1;baz-2 and blmp-1;set-6 double mutant worms were obtained and their lifespan,pharyngeal pumping,basal and enhanced slowing responses,capacity of oxidative resistance and the expression of nuclear genes encoding mitochondrial proteins were analyzed.The results show that ablation of blmp-1 abolishes the lifespan extension,behavioral preservation and up-regulated expression of nuclear genes encoding mitochondrial proteins in aging baz-2 or set-6 mutant worms.This study suggests that BAZ-2 and SET-6 modulate aging via BLMP-1 in C.elegans.