DNA (cytosine-5)-methyltransferase 3B (DNA methyltransferase-3B) or DNA methyltransferase HsaIIIB

Function

• responsible for genome wide de novo methylation in mammals
• essential for the establishment of DNA methylation patterns during development
• may preferentially methylate nucleosomal DNA within the nucleosome core region
• may function as transcriptional co-repressor by associating with CBX4
• seems to be involved in gene silencing
• involved in activation of BAG1 gene expression by modulating dimethylation of promoter histone H3 at H3K4 & H3K9 (DNMT1 & CTCFL/BORIS may be involved)
• isoforms 4 & 5 are probably not functional due to the deletion of two conserved methyltransferase motifs
• activated by binding to the regulatory factor DNMT3L (putative)
• sumoylated
• interacts with BAZ2A/TIP5, SUV39H1 & CBX4
• interacts with SETDB1, UBL1 & UBE2I9
• interacts with DNMT1 & DNMT3A
• interacts with the PRC2/EED-EZH2 complex

S-adenosyl-L-methionine + DNA = S-adenosyl-L-homocysteine + DNA containing 5-methylcytosine

Structure

• the PWWP domain is essential for targeting to pericentric heterochromatin
• belongs to the C5-methyltransferase family
• contains 1 ADD-type Zn+2 finger
• contains 1 PWWP domain

Compartment

nucleus

Alternative splicing

named isoforms=6

Expression

• ubiquitous
• highly expressed in fetal liver, heart, kidney, placenta
• lower levels in spleen, colon, brain, liver, small intestine, lung, peripheral blood mononuclear cells, & skeletal muscle
• isoform 1 is expressed in all tissues except brain, skeletal muscle & PBMC
• isoform 3 is ubiquitous
• isoform 4 is expressed in all tissues except brain, skeletal muscle, lung & prostate
• isoform 5 is detectable in testis & at very low level in brain & prostate

Pathology

• defects associated with immunodeficiency centromeric instability-facial anomalies (ICF) syndrome.

More general terms

• DNA (cytosine-5)-methyltransferase

Database

• Entrez gene: http://www.ncbi.nlm.nih.gov/sites/entrez?db=gene&cmd=Retrieve&dopt=Graphics&list_uids=1789
• Kegg: http://www.genome.jp/dbget-bin/www_bget?hsa:1789
• OMIM: https://mirror.omim.org/entry/242860
• OMIM: https://mirror.omim.org/entry/602900
• UniProt: http://www.uniprot.org/uniprot/Q9UBC3.html