Vitamin B₁₂ is a limiting factor for induced cellular plasticity and tissue repair.

ABSTRACT: Transient reprogramming by the expression of OCT4, SOX2, KLF4 and MYC (OSKM) is a therapeutic strategy for tissue regeneration and rejuvenation, but little is known about its metabolic requirements. Here we show that OSKM reprogramming in mice causes a global depletion of vitamin B₁₂ and molecular hallmarks of methionine starvation. Supplementation with vitamin B₁₂ increases the efficiency of reprogramming both in mice and in cultured cells, the latter indicating a cell-intrinsic effect. We show that the epigenetic mark H3K36me3, which prevents illegitimate initiation of transcription outside promoters (cryptic transcription), is sensitive to vitamin B₁₂ levels, providing evidence for a link between B₁₂ levels, H3K36 methylation, transcriptional

SUBMITTER: Kovatcheva M 

PROVIDER: S-EPMC10663163 | biostudies-literature | 2023 Nov

REPOSITORIES: biostudies-literature