Tet2 regulates Barx2 expression in undifferentiated and early differentiated mouse embryonic stem cells

The methylcytosine oxidase TET proteins play important roles in DNA demethylation and development. In developing embryos, TET2 are upregulated during pre-implantation development, and significantly expressed in the trophectoderm and inner cell mass. In this study, we identified Barx2 as a new target of Tet2. Tet2 bound and demethylated the promoter of Barx2 in mouse embryonic stem cells (mESCs) to maintain the expression of Barx2. During mESC differentiation, Tet2 bound the promoter of Barx2 in day 4 embryonic bodies but not in day 8 EBs. However, Barx2 expression remained unchanged. Thus, Tet2 functioned as a demethylase and maintained the expression of Barx2 in undifferentiated and early differentiated mESCs. •Tet2 showed genome-wide binding in transcription regulation and developmental genes.•Barx2 was the key node in the network of downregulated genes upon Tet2 depletion.•Tet2 reduced methylation in the promoter of Barx2 and upregulated Barx2.•Tet2 could also regulate the methylation of Barx2 promoter in early differentiation mESC.