Distinct catalytic-dependent or -independent activities of DNMT1 in mouse embryonic stem cells

DNMT1 maintains DNA methylation profile and regulates gene expression. Although DNMT1 interacts with other proteins that regulate gene expressions, it remains unclear how the protein-protein interaction or the catalytic activity of DNMT1 itself affect gene expression and DNA methylation pattern. In this study, immunofluorescence staining showed abnormal DNA methylation pattern in chromosome arms of DNMT1-deficient (1KO) mouse embryonic stem cells (ESCs), and we hypothesized that DNMT1 helps methylation activity of DNMT3. To validate this hypothesis, we generate transgenic 1KO ESCs expressing catalytic inactive DNMT1 (1KO+1CI). Here, we used RNA-seq to analyze the effect of catalytic-dependent or -independent DNMT1 activity on gene expression in ESCs or epiblast-like cells (EpiLCs) induction. Overall design: RNA-seq was performed on WT and 1KO, 1KO+1CI ESCs in their undifferentiated state (d0) and during the induction of EpiLCs differentiation (d2 and d4).