Dnmt3b, a DNA methyltransferase, is crucial for de novo methylation, a process essential for establishing DNA methylation patterns predominantly during early development and gametogenesis in mice [1]. It belongs to the DNMT3 family and, along with Dnmt3a, is vital for normal mammalian development. DNA methylation, regulated by Dnmt3b, plays a significant role in gene expression regulation, chromatin structure, and cellular differentiation [2].

Gene targeting inactivation of Dnmt3b and Dnmt3a in ES cells and early embryos blocks de novo methylation, highlighting their essential function in this process [1]. In Dnmt3b knockout (3BKO) mouse models, there are impairments in the differentiation of epiblast-like cells (EpiLCs) into meso-endodermal (ME) progenitors, with EpiLCs redirected towards neuro-ectodermal lineages [4]. Also, Dnmt3b knockout cells show R-loop-mediated DNA damage at satellite repetitive DNA sequences including (peri -) centromere regions, undermining centromere integrity [3]. Mutations in human DNMT3B are associated with ICF syndrome, characterized by hypomethylation of pericentromeric repeats [1,2].

In summary, Dnmt3b is essential for de novo methylation, normal development, and maintaining centromere integrity. Studies using Dnmt3b KO mouse models have provided insights into its role in cell fate determination during development and its association with diseases like ICF syndrome. Understanding Dnmt3b's functions contributes to our knowledge of normal biological processes and disease mechanisms.

References:

1. Okano, M, Bell, D W, Haber, D A, Li, E. . DNA methyltransferases Dnmt3a and Dnmt3b are essential for de novo methylation and mammalian development. In Cell, 99, 247-57. doi:. https://pubmed.ncbi.nlm.nih.gov/10555141/

2. Gagliardi, Miriam, Strazzullo, Maria, Matarazzo, Maria R. 2018. DNMT3B Functions: Novel Insights From Human Disease. In Frontiers in cell and developmental biology, 6, 140. doi:10.3389/fcell.2018.00140. https://pubmed.ncbi.nlm.nih.gov/30406101/

3. Shih, Hsueh-Tzu, Chen, Wei-Yi, Wang, Hsin-Yen, Chou, Chih-Hung, Chang, Zee-Fen. 2022. DNMT3b protects centromere integrity by restricting R-loop-mediated DNA damage. In Cell death & disease, 13, 546. doi:10.1038/s41419-022-04989-1. https://pubmed.ncbi.nlm.nih.gov/35688824/

4. Lauria, Andrea, Meng, Guohua, Proserpio, Valentina, Neri, Francesco, Oliviero, Salvatore. 2023. DNMT3B supports meso-endoderm differentiation from mouse embryonic stem cells. In Nature communications, 14, 367. doi:10.1038/s41467-023-35938-x. https://pubmed.ncbi.nlm.nih.gov/36690616/