DNA (cytosine-5)-methyltransferase 3 beta (DNMT3B)

DNA (cytosine‐5)‐methyltransferase 3 beta (DNMT3B) is an enzyme encoded by the DNMT3B gene. It catalyzes de novo cytosine methylation at CpG sites across the genome—a key epigenetic modification required for embryonic development, X-chromosome inactivation, imprinting, chromatin structure maintenance, and long-term transcriptional repression. Unlike maintenance methyltransferases such as DNMT1, which preserve existing patterns after replication, DNMT3B establishes new patterns during early development. Mutations cause immunodeficiency-centromeric instability-facial anomalies syndrome (ICF syndrome) due to defective lymphocyte maturation from aberrant DNA methylation. Overexpression or dysregulation contributes directly to oncogenesis by promoting abnormal gene silencing—especially tumor suppressor genes—and supports cancer cell survival. As such, it has emerged as both a biomarker and therapeutic target across several malignancies including multiple myeloma. Pharmacologic inhibition aims either at reversing pathological hypermethylation or sensitizing tumors resistant to standard therapies; however, safety concerns remain regarding potential disruption of normal epigenetic programming.

Other names

DNMT3BDNA methyltransferase HsaIIIBDNA MTase HsaIIIBDnmt3bM.HsaIIIB

Drugs targeting DNMT3B generally act as inhibitors, blocking its ability to catalyze the transfer of a methyl group to cytosine residues in DNA. This leads to hypomethylation, reactivation of silenced genes (including tumor suppressors), and can induce apoptosis in cancer cells where DNMT3B is essential for survival.