Dnmt1-flox Mouse

Dnmt1, DNA methyltransferase 1, is the predominant member of the DNMT family and the most abundant DNMT in various cell types. It functions as a maintenance DNMT, playing a crucial role in regulating DNA methylation, which is involved in multiple biological processes such as chromatin organization, DNA repair, cell cycle regulation, and apoptosis [2,3].

In triple-negative breast cancer (TNBC), Dnmt1 is overexpressed and associated with poor survival. It represses estrogen receptor (ER) expression, promotes epithelial-mesenchymal transition (EMT) for metastasis, induces cellular autophagy, and promotes the growth of cancer stem cells by hypermethylating relevant promoter regions [1]. In human erythropoiesis, Dnmt1 deficiency leads to cell cycle arrest of erythroid progenitors due to decreased DNA methylation of the p21 promoter and increased apoptosis during the terminal stage by inducing endoplasmic reticulum (ER) stress [4]. In esophageal cancer, Dnmt1 negatively correlates with FBXO32 expression, and its enrichment in the FBXO32 promoter region leads to increased DNA methylation and reduced transcription, promoting cancer cell growth [5].

In conclusion, Dnmt1 is essential for maintaining normal DNA methylation patterns and is involved in numerous biological processes. Studies, including those using potential gene knockout models inferred from the functional impacts observed, have revealed its significant roles in cancer development such as in TNBC, esophageal cancer, and in processes like erythropoiesis. Understanding Dnmt1 provides insights into disease mechanisms and potential therapeutic targets.