Comparison of heat responsive gene expression after histone methyltransferase RNAi in C. elegans. Comparison of heat responsive gene expression after histone methyltransferase RNAi in C. elegans

We resport the changes in gene expression occuring after heat exposure in C. elegans with low s-adenosylmethionine, or RNAi of two H3K4 methyltransferases Using a C. elegans model of low SAM, we previously found that transcriptional responses response to a bacterial pathogen failed and these bacterial-response genes did not show normal H3K4me3 close to the transcriptional start sites, (Ding et al. 2015 Cell Metabolism). We also found the HMT set-16/MLL was required for full induction, whereas set-2/SET1 appeared dispensable (Ding et al. 2015 Cell Metabolism). We hypothesized that animals with low SAM might fail to transcriptionally respond to stress and that the HMTs may also have distinct roles in modulating stress responses. In our present study, we set out to compare induction of transcriptional responses and survival upon stress exposure between C. elegans with reduced SAM (sams-1(RNAi)) and animals with limited H3K4me3 function, set-2/SET1, and set-16/MLL RNAi. Because distinct stresses may rely on different transcriptional activation mechanisms, we also compared whole-genome expression patterns in three stresses: pathogenic bacteria (PA14), xenotoxic (R24) and heat in response to each RNAi. Overall design: C. elegans were grown on RNAi plates, then exposed to 37°C for 90 minutes

本数据集报道了低S-腺苷甲硫氨酸（S-adenosylmethionine, SAM）水平的秀丽隐杆线虫（Caenorhabditis elegans, C. elegans），或经两种H3K4甲基转移酶（H3K4 methyltransferases）RNA干扰（RNA interference, RNAi）处理的线虫，在热暴露后发生的基因表达变化。我们此前利用低SAM水平的秀丽隐杆线虫模型开展研究，发现其对细菌病原体的转录应答失效，且这类细菌应答基因在转录起始位点附近未呈现正常的H3K4me3修饰（Ding等，2015，《Cell Metabolism》）。我们同时发现，组蛋白甲基转移酶（Histone Methyltransferase, HMT）set-16/MLL对于基因的完全诱导是必需的，而set-2/SET1则似乎并非不可或缺（Ding等，2015，《Cell Metabolism》）。基于上述发现，我们提出假说：低SAM水平的线虫可能无法对胁迫产生转录层面的应答，且不同的HMT在调控胁迫应答过程中可能发挥截然不同的功能。在本研究中，我们旨在对比两类秀丽隐杆线虫在胁迫暴露后的转录应答诱导情况与存活率：一类为SAM水平降低的线虫（sams-1(RNAi)），另一类为H3K4me3功能受限的线虫，即分别通过RNA干扰抑制set-2/SET1与set-16/MLL表达的个体。由于不同的胁迫可能依赖不同的转录激活机制，我们还针对每种RNA干扰处理，比较了三种胁迫条件下的全基因组表达谱：病原菌胁迫（PA14）、外源毒性胁迫（R24）以及热胁迫。实验整体设计：将秀丽隐杆线虫培养于RNA干扰平板中，随后置于37℃环境下暴露90分钟。