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Polyamine metabolism regulates the T cell epigenome through hypusination

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Mus musculus

PROVIDER: GSE157598 | GEO | 2021/07/07

REPOSITORIES: GEO

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Polyamine metabolism regulates the T cell epigenome through hypusination [RNA-seq]

Project description:We report here a central role for polyamines in T cell differentiation and function. Deficiency in ornithine decarboxylase (ODC), a critical enzyme for polyamine synthesis, resulted in a profound failure of CD4+ T cells to adopt correct subset specification, underscored by ectopic expression of multiple cytokines and lineage- defining transcription factors across TH1, TH2, TH17, and Treg polarizing conditions, and enhanced colitogenic potential. T cells deficient in deoxyhypusine synthase (DHPS) or deoxyhypusine hydroxylase (DOHH), which sequentially utilize polyamines to generate hypusine, phenocopied Odc-deficient T cells, and mice in which T cells lacked Dhps or Dohh developed colitis. Polyamine-hypusine pathway enzyme deficiency caused widespread chromatin and transcriptional dysregulation accompanied by alterations in histone methylation, histone acetylation, and TCA cycle metabolites. Epigenetic modulation by 2-hydroxyglutarate, or histone acetyltransferase inhibition, restored CD4+ T cell subset specification. Thus, polyamine synthesis via hypusine is critical for maintaining the epigenome to focus TH cell subset fidelity.

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Polyamine metabolism regulates the T cell epigenome through hypusination [ATAC-seq]

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