生物
磷脂酰乙醇胺
甲基化
生物化学
组蛋白甲基化
磷脂
甲基转移酶
组蛋白
组蛋白甲基转移酶
DNA甲基化
EZH2型
细胞生物学
磷脂酰胆碱
基因表达
DNA
基因
膜
作者
Cunqi Ye,Benjamin M. Sutter,Yun Wang,Zheng Kuang,Benjamin P. Tu
出处
期刊:Molecular Cell
[Elsevier]
日期:2017-04-01
卷期号:66 (2): 180-193.e8
被引量:191
标识
DOI:10.1016/j.molcel.2017.02.026
摘要
S-adenosylmethionine (SAM) is the methyl donor for biological methylation modifications that regulate protein and nucleic acid functions. Here, we show that methylation of a phospholipid, phosphatidylethanolamine (PE), is a major consumer of SAM. The induction of phospholipid biosynthetic genes is accompanied by induction of the enzyme that hydrolyzes S-adenosylhomocysteine (SAH), a product and inhibitor of methyltransferases. Beyond its function for the synthesis of phosphatidylcholine (PC), the methylation of PE facilitates the turnover of SAM for the synthesis of cysteine and glutathione through transsulfuration. Strikingly, cells that lack PE methylation accumulate SAM, which leads to hypermethylation of histones and the major phosphatase PP2A, dependency on cysteine, and sensitivity to oxidative stress. Without PE methylation, particular sites on histones then become methyl sinks to enable the conversion of SAM to SAH. These findings reveal an unforeseen metabolic function for phospholipid and histone methylation intrinsic to the life of a cell.
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