DNA (cytosine-5)-methyltransferase 1; Dnmt1; CXXC-type zinc finger protein 9; DNA methyltransferase HsaI; DNA MTase HsaI; M.HsaI; MCMT (DNMT1 AIM CXXC9 DNMT)
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Function
- responsible for cytosine methylation in mammals
- methylates CpG residues
- catalyzes S-adenosylmethionine (SAM)-mediated methylation of cytosine to form 5'methyl-deoxycytosine in CpG islands
- preferentially methylates hemimethylated DNA
- associates with DNA replication sites in S phase maintaining the methylation pattern in the newly synthesized strand, that is essential for epigenetic inheritance
- associates with chromatin during G2 & M phases to maintain DNA methylation independently of replication
- responsible for maintaining methylation patterns established in development
- DNA methylation is coordinated with methylation of histones
- mediates transcriptional repression by direct binding to HDAC2
- in association with DNMT3B & via the recruitment of CTCFL/BORIS, involved in activation of BAG1 gene expression by modulating dimethylation of promoter histone H3 at H3K4 & H3K9
- sumoylated; sumoylation increases activity
- interacts with HDAC1 & with PCNA
- forms a complex with DMAP1 & HDAC2, with direct interaction
- forms also a stable complex with E2F1, BB1 & HDAC1
- binds MBD2 & MBD3 component of complexes containing SUV39H1
- interacts with DNMT3A & DNMT3B
- interacts with the PRC2/EED-EZH2 complex
- interacts with UBC9 & BAZ2A/TIP5
S-adenosyl-L-methionine + DNA = S-adenosyl-L-homocysteine + DNA containing 5-methylcytosine
Structure
- homodimer
- the binding site for histone deacetylase-1, referred to as a transcriptional repressor domain in ref 2, shows homology to the transcriptional repressor gene of the zinc finger protein HRX (MLL, ALL-1)
Compartment
Alternative splicing
named isoforms=3
Expression
- ubiquitous
- highly expressed in fetal tissues, heart, kidney, placenta, peripheral blood mononuclear cells
- expressed at lower levels in spleen, lung, brain, small intestine, colon, liver, & skeletal muscle
- isoform 2 is less expressed than isoform 1
- expression is reduced to non-detectable levels in G0 phase of the cell cycle
- expression is induced upon entrance into the S-phase of the cell cycle
Genetics
- other DNA methyltransferases are apparently active in human cells
- evidence using recombinant human colorectal cells suggests that most loci remain fully methylated in the absence of DNA methyltransferase-1 (only juxtacentromeric satellite DNA became significantly demethylated).
More general terms
Additional terms
- CpG island, GC-rich element or GC box
- DNA methylation (promoter methylation)
- histone deacetylase 1 (reduced potassium dependency 3 [RPD3] homolog-like 1, HDAC1, RPD3L1)
- histone-lysine N-methyltransferase 2A
References
- ↑ UniProt http://www.uniprot.org/uniprot/P26358.html
- ↑ Atlas of Genetics & Cytogenetics in Oncology & Haematology http://atlasgeneticsoncology.org/genes/DNMT1ID40347ch19p13.html
- ↑ Fuks F et al DNA methyltransferase Dnmt1 associates with histone deacetylase activity. Nature Genetics 24:88, 2000 PMID: https://www.ncbi.nlm.nih.gov/pubmed/10615135
- ↑ Rhee I et al CpG methylation is maintained in human cancer cells lacking DNMT1. Nature 404:1003, 2000 PMID: https://www.ncbi.nlm.nih.gov/pubmed/10801130