Methionine metabolism is essential for SIRT1-regulated mouse embryonic stem cell maintenance and embryonic development.

ABSTRACT: Methionine metabolism is critical for epigenetic maintenance, redox homeostasis, and animal development. However, the regulation of methionine metabolism remains unclear. Here, we provide evidence that SIRT1, the most conserved mammalian NAD⁺-dependent protein deacetylase, is critically involved in modulating methionine metabolism, thereby impacting maintenance of mouse embryonic stem cells (mESCs) and subsequent embryogenesis. We demonstrate that SIRT1-deficient mESCs are hypersensitive to methionine restriction/depletion-induced differentiation and apoptosis, primarily due to a reduced conversion of methionine to S-adenosylmethionine. This reduction markedly decreases methylation levels of histones, resulting in dramatic alterations in gene expression profiles. Mechanistically

SUBMITTER: Tang S 

PROVIDER: S-EPMC5666621 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature