C5-cytosine DNA methyltransferase-3A; DNA (cytosine-5)-methyltransferase 3A; Dnmt3a; DNA methyltransferase HsaIIIA; DNA MTase HsaIIIA; M.HsaIIIA (DNMT3A)
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Function
- responsible for genome wide de novo methylation in mammals
- catalyzes S-adenosylmethionine (SAM)-mediated methylation of cytosine to form 5-methylcytosine + S-adenosyl-l-homocysteine
- essential for the establishment of DNA methylation patterns during development
- DNA methylation is coordinated with methylation of histones
- modifies DNA in a non-processive manner & also methylates non-CpG sites
- may preferentially methylate DNA linker between 2 nucleosomal cores & is inhibited by histone H1
- role in paternal & maternal imprinting
- required for methylation of most imprinted loci in germ cells
- acts as a transcriptional corepressor for ZNF238
- can actively repress transcription through the recruitment of HDAC activity
- activated by binding to the regulatory factor DNMT3L (putative)
- sumoylated; sumoylation disrupts the ability to interact with histone deacetylases (HDAC1 & HDAC2) & represses transcription
- heterotetramer composed of 1 DNMT3A homodimer & 2 DNMT3L subunits (DNMT3L-DNMT3A-DNMT3A-DNMT3L)
- interacts with UBC9, PIAS1 & PIAS2 (putative)
- binds the ZNF238 transcriptional repressor
- interacts with SETDB1
- associates with HDAC1 through its ADD-type Zn+2-finger (putative)
- interacts with DNMT1 & DNMT3B
- 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, cytoplasm
- accumulates in the major satellite repeats at pericentric heterochromatin
Alternative promoter usage
named isoforms=2
Expression
- highly expressed in fetal tissues, skeletal muscle, heart, peripheral blood mononuclear cells, kidney
- expressed at lower levels in placenta, brain, liver, colon, spleen, small intestine & lung