Glis1 Activate Glycolytic Process and Increase H3K27Ac Level on Pluripotent and Second Wave Genes Promoter Facilitating Pluripotency Induction [RNA-Seq]

Metabolic activity possess a crucial role during cell fate determination. Here, we show that maternal transcriptional factor Glis1 could not only promote normal MEF reprogramming but also enable aging MEF reprogramming. By association ChIP-seq and RNA-seq, we found that Glis1 could bind and activate glycolytic genes, and bind and suppress somatic state genes simultaneously during reprogramming. While knockdown phosphoglyceric kinase (Pgk1) impeded reprogramming efficiency which indicates that Glis1-glycolytic process axes is required for Glis1 function. Metabolic analysis indicated that the level of acetyl-CoA has a significant fluctuation upon Glis1 induction or silence. Acetate, a precursor of acetyl-CoA rescued the effects on reprogramming in a time-dependent manner when knockdown endogenous Glis1. The fluctuation of Ac-CoA changed the level of H3K27Ac, especially in pluripotent genes and “second wave” genes promoter, and activated the expression of endogenous pluripotency genes in advance subsequently. In conclusion, we demonstrate the exactly novel mechanism of Glis1 in pluripotency acquisition. reprogramming cell mRNA profiles of day8 SKO+Flag and SKO+Glis1 were generated by deep sequencin, using Illumina Hiseq 4000.