Dnmt3b is a key de novo DNA methyltransferase. DNA methylation, regulated by Dnmt3b along with other DNA methyltransferases, is crucial for establishing DNA methylation patterns, which is essential for mammalian development, cellular differentiation, and gene expression regulation [1,2].

In gene-targeting knockout mouse models, inactivation of Dnmt3b, along with Dnmt3a, blocks de novo methylation in embryonic stem (ES) cells and early embryos, indicating its essential role in de novo methylation. Specifically, Dnmt3b is required for the methylation of centromeric minor satellite repeats [1]. In cells with Dnmt3b knockout or in immunodeficiency-centromeric instability-facial anomalies (ICF) syndrome cells with Dnmt3b functional loss mutations, R-loops contribute to DNA damages, and the integrity of centromere is undermined, suggesting Dnmt3b protects centromere integrity by restricting R-loop-mediated DNA damage [3]. Also, in Dnmt3b knockout mouse embryonic stem cells, the differentiation into meso-endodermal progenitors is impaired, redirecting cells towards the neuro-ectodermal lineages, showing that Dnmt3b-dependent methylation at the epiblast stage is essential for priming meso-endodermal lineages [4].

In conclusion, Dnmt3b is vital for de novo DNA methylation, especially in early development. Studies using Dnmt3b knockout mouse models have revealed its roles in maintaining centromere integrity and cell lineage differentiation. Abnormalities in Dnmt3b function are associated with diseases like ICF syndrome, highlighting its significance in understanding disease mechanisms [1,2,3,4].