Program in Molecular Medicine, UMASS Medical School, Worcester, MA, United States of America.
Department of Computer Sciences, Georgia Institute of Technology, Atlanta, GA, United States of America.
PLoS Genet. 2018 Nov 28;14(11):e1007812. doi: 10.1371/journal.pgen.1007812. eCollection 2018 Nov.
S-adenosylmethionine (SAM) is a donor which provides the methyl groups for histone or nucleic acid modification and phosphatidylcholine production. SAM is hypothesized to link metabolism and chromatin modification, however, its role in acute gene regulation is poorly understood. We recently found that Caenorhabditis elegans with reduced SAM had deficiencies in H3K4 trimethylation (H3K4me3) at pathogen-response genes, decreasing their expression and limiting pathogen resistance. We hypothesized that SAM may be generally required for stress-responsive transcription. Here, using genetic assays, we show that transcriptional responses to bacterial or xenotoxic stress fail in C. elegans with low SAM, but that expression of heat shock genes are unaffected. We also found that two H3K4 methyltransferases, set-2/SET1 and set-16/MLL, had differential responses to survival during stress. set-2/SET1 is specifically required in bacterial responses, whereas set-16/MLL is universally required. These results define a role for SAM in the acute stress-responsive gene expression. Finally, we find that modification of metabolic gene expression correlates with enhanced survival during stress.
S-腺苷甲硫氨酸（SAM）是一种供体，可为组蛋白或核酸修饰以及磷脂酰胆碱的生成提供甲基。SAM 被假设可以将代谢和染色质修饰联系起来，但是，其在急性基因调控中的作用还知之甚少。我们最近发现，SAM 减少的秀丽隐杆线虫在病原体反应基因处的 H3K4 三甲基化（H3K4me3）不足，从而降低了它们的表达并限制了病原体的抗性。我们假设 SAM 可能普遍需要应激反应转录。在这里，我们使用遗传分析表明，在 SAM 含量低的线虫中，细菌或细胞毒性应激的转录反应失败，但是热休克基因的表达不受影响。我们还发现，两种 H3K4 甲基转移酶，set-2/SET1 和 set-16/MLL，对生存过程中的应激有不同的反应。set-2/SET1 在细菌反应中特异性需要，而 set-16/MLL 则普遍需要。这些结果定义了 SAM 在急性应激反应基因表达中的作用。最后，我们发现代谢基因表达的修饰与应激期间的生存能力增强相关。
