A Metabolic Function for Phospholipid and Histone Methylation

Cunqi Ye, Benjamin M. Sutter, Yun Wang, Zheng Kuang, Benjamin P. Tu

Research output: Contribution to journalArticlepeer-review

63 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)180-193.e8
JournalMolecular cell
Volume66
Issue number2
DOIs
StatePublished - Apr 20 2017

Keywords

  • H3K36
  • S-adenosylmethionine
  • cysteine
  • epigenetics
  • glutathione
  • histone methylation
  • methyltransferase
  • phospholipids
  • transsulfuration

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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