Required for genome-wide de novo methylation and is essential for the establishment of DNA methylation patterns during development. DNA methylation is coordinated with methylation of histones. May preferentially methylates nucleosomal DNA within the nucleosome core region. May function as transcriptional co-repressor by associating with CBX4 and independently of DNA methylation. Seems to be involved in gene silencing (By similarity). In association with DNMT1 and via the recruitment of CTCFL/BORIS, involved in activation of BAG1 gene expression by modulating dimethylation of promoter histone H3 at H3K4 and H3K9. Isoforms 4 and 5 are probably not functional due to the deletion of two conserved methyltransferase motifs. Functions as a transcriptional corepressor by associating with ZHX1. Required for DUX4 silencing in somatic cells (PubMed:27153398). a 2'-deoxycytidine in DNA + S-adenosyl-L-methionine = a 5-methyl-2'-deoxycytidine in DNA + H(+) + S-adenosyl-L-homocysteine Activated by binding to the regulatory factor DNMT3L. Interacts with BAZ2A/TIP5, SUV39H1 and CBX4. Interacts with UHRF1 (By similarity). Interacts with DNMT1 and DNMT3A, SETDB1, UBL1, UBE2I9 and ZHX1. Interacts with the PRC2/EED-EZH2 complex. Ubiquitous; highly expressed in fetal liver, heart, kidney, placenta, and at lower levels in spleen, colon, brain, liver, small intestine, lung, peripheral blood mononuclear cells, and skeletal muscle. Isoform 1 is expressed in all tissues except brain, skeletal muscle and PBMC, 3 is ubiquitous, 4 is expressed in all tissues except brain, skeletal muscle, lung and prostate and 5 is detectable only in testis and at very low level in brain and prostate. The PWWP domain is essential for targeting to pericentric heterochromatin. Sumoylated. Citrullinated by PADI4. The disease is caused by variants affecting the gene represented in this entry. The disease is caused by variants affecting distinct genetic loci, including the gene represented in this entry. DNMT3B mutations lead to DUX4 expression in somatic tissues, including muscle cells, when an haplotype on chromosome 4 is permissive for DUX4 expression. Ectopic expression of DUX4 in skeletal muscle activates the expression of stem cell and germline genes, and, when overexpressed in somatic cells, DUX4 can ultimately lead to cell death. Belongs to the class I-like SAM-binding methyltransferase superfamily. C5-methyltransferase family. DNMT3B mutation db