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Glycolysis regulates gene expression by promoting the crosstalk between H3K4 trimethylation and H3K14 acetylation in Saccharomyces cerevisiae.
Journal of Genetics and Genomics ( IF 6.6 ) Pub Date : 2019-12-11 , DOI: 10.1016/j.jgg.2019.11.007
Yinsheng Wu 1 , Shihao Zhang 1 , Xuanyunjing Gong 1 , Qi Yu 1 , Yuan Zhang 1 , Mingdan Luo 1 , Xianhua Zhang 1 , Jerry L Workman 2 , Xilan Yu 1 , Shanshan Li 1
Affiliation  

Cells need to coordinate gene expression with their metabolic states to maintain cell homeostasis and growth. However, how cells transduce nutrient availability to appropriate gene expression response via histone modifications remains largely unknown. Here, we report that glucose specifically induces histone H3K4 trimethylation (H3K4me3), an evolutionarily conserved histone covalent modification associated with active gene transcription, and that glycolytic enzymes and metabolites are required for this induction. Although glycolysis supplies S-adenosylmethionine for histone methyltransferase Set1 to catalyze H3K4me3, glucose induces H3K4me3 primarily by inhibiting histone demethylase Jhd2-catalyzed H3K4 demethylation. Glycolysis provides acetyl-CoA to stimulate histone acetyltransferase Gcn5 to acetylate H3K14, which then inhibits the binding of Jhd2 to chromatin to increase H3K4me3. By repressing Jhd2-mediated H3K4 demethylation, glycolytic enzymes regulate gene expression and cell survival during chronological aging. Thus, our results elucidate how cells reprogram their gene expression programs in response to glucose availability via histone modifications.



中文翻译:

在酿酒酵母中,糖酵解通过促进 H3K4 三甲基化和 H3K14 乙酰化之间的串扰来调节基因表达。

细胞需要协调基因表达与其代谢状态,以维持细胞稳态和生长。然而,细胞如何通过组蛋白修饰将营养物质可用性转变成适当的基因表达反应仍然很大程度上未知。在这里,我们报告葡萄糖特异性诱导组蛋白 H3K4 三甲基化 (H3K4me3),这是一种与活跃基因转录相关的进化上保守的组蛋白共价修饰,并且这种诱导需要糖酵解酶和代谢物。尽管糖酵解为组蛋白甲基转移酶 Set1 提供 S-腺苷甲硫氨酸以催化 H3K4me3,但葡萄糖主要通过抑制组蛋白去甲基化酶 Jhd2 催化的 H3K4 去甲基化来诱导 H3K4me3。糖酵解提供乙酰辅酶A刺激组蛋白乙酰转移酶Gcn5乙酰化H3K14,然后抑制Jhd2与染色质的结合以增加H3K4me3。通过抑制 Jhd2 介导的 H3K4 去甲基化,糖酵解酶可调节衰老过程中的基因表达和细胞存活。因此,我们的结果阐明了细胞如何通过组蛋白修饰重新编程其基因表达程序以响应葡萄糖的可用性。

更新日期:2019-12-11
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