S-adenosylmethionine synthases specify distinct H3K4me3 populations and gene expression patterns during heat stress.
S-adenosylmethionine synthases specify distinct H3K4me3 populations and gene expression patterns during heat stress.
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DOI：
10.7554/elife.79511
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发表时间：
2023-02-09
期刊：
影响因子：
7.7
通讯作者：
Walker AK
中科院分区：
文献类型：
--
作者：
Godbole AA;Gopalan S;Nguyen TK;Munden AL;Lui DS;Fanelli MJ;Vo P;Lewis CA;Spinelli JB;Fazzio TG;Walker AK
甲基化是一种广泛存在的修饰，需要甲基供体S-腺苷甲硫氨酸（SAM），并在基因表达和其他过程的调控中起作用。SAM是由蛋氨酸合成的，蛋氨酸是通过1-碳循环（1 CC）输入或产生的。1 CC功能的改变对寿命和应激反应有明显的影响，但这种修饰的广泛分布使识别特定的机制联系变得困难。利用动态应激诱导的转录模型，我们发现秀丽隐杆线虫中的两种SAM酶，SAMS-1和SAMS-4，对H3 K4 me 3的修饰、基因表达和存活有不同的贡献。我们发现，在缺乏sams-1的热休克动物中，sams-4增强H3 K4 me 3，然而，sams-1不能补偿sams-4，这是在热应激中生存所必需的。这表明SAM的调节功能依赖于其酶源，SAM的供应可能是将1 CC功能与衰老和应激中的表型联系起来的重要调节步骤。
Methylation is a widely occurring modification that requires the methyl donor S-adenosylmethionine (SAM) and acts in regulation of gene expression and other processes. SAM is synthesized from methionine, which is imported or generated through the 1-carbon cycle (1 CC). Alterations in 1 CC function have clear effects on lifespan and stress responses, but the wide distribution of this modification has made identification of specific mechanistic links difficult. Exploiting a dynamic stress-induced transcription model, we find that two SAM synthases in Caenorhabditis elegans, SAMS-1 and SAMS-4, contribute differently to modification of H3K4me3, gene expression and survival. We find that sams-4 enhances H3K4me3 in heat shocked animals lacking sams-1, however, sams-1 cannot compensate for sams-4, which is required to survive heat stress. This suggests that the regulatory functions of SAM depend on its enzymatic source and that provisioning of SAM may be an important regulatory step linking 1 CC function to phenotypes in aging and stress.