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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)

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: nucleus 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).

Related

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; lysine N-methyltransferase 2A; ALL-1; CXXC-type zinc finger protein 7; myeloid/lymphoid or mixed-lineage leukemia protein 1; trithorax-like protein; zinc finger protein HRX; contains: MLL cleavage product N320; N-terminal cleavage product of 320 kDa; p320; contains: MLL cleavage product C180; C-terminal cleavage product of 180 kD; p180 (KMT2A, ALL1, CXXC7, HRX, HTRX, MLL, MLL1)

General

DNA (cytosine-5)-methyltransferase phosphoprotein zinc finger protein

Properties

SIZE: entity length = 1616 aa MW = 183 kD COMPARTMENT: cell nucleus MOTIF: PRC2/EED-EZH2interaction {1-336} MOTIF: DNMT3A interaction {1-148} DMAP1 interaction {1-120} Ser phosphorylation site {S127} Thr phosphorylation site {T137} DNMT3B interaction {149-217} Ser phosphorylation site {S152} Ser phosphorylation site {S154} PCNA interaction {163-174} nuclear translocation signal {177-205} Ser phosphorylation site {S288} PRC2/EED-EZH2 interaction {308-606} MOTIF: Homodimerization {310-502} domain {331-550} Zn+2-binding site SITE: 353-353 Zn+2-binding site SITE: 356-356 Ser phosphorylation site {S394} Zn+2-binding site SITE: 414-414 Zn+2-binding site SITE: 418-418 serine residue {509} Ser phosphorylation site {S509} Zinc finger NAME: Zinc finger SITE: 646-692 EFFECTOR-BOUND: Zn+2 activity {651-697} Ser phosphorylation site {S714} Ser phosphorylation site {S732} BAH 1 {755-880} Ser phosphorylation site {S954} Tyr phosphorylation site {Y969} BAH 2 {972-1100} Ser phosphorylation site {S1105} tandem repeats of K-G {1109-1120} MOTIF: consensus repeat {1109-1110} consensus repeat {1111-1112} consensus repeat {1113-1114} consensus repeat {1115-1116} consensus repeat {1117-1118} consensus repeat {1119-1120} PRC2/EED-EZH2 interaction {1121-1616} MOTIF: active site SITE: 1139-1616 cysteine residue {C1226}

Database Correlations

OMIM 126375 UniProt P26358 PFAM correlations Entrez Gene 1786 KEGG correlations ENZYME 2.1.1.73

References

  1. UniProt :accession P26358
  2. Atlas of Genetics & Cytogenetics in Oncology & Haematology http://atlasgeneticsoncology.org/genes/DNMT1ID40347ch19p13.html
  3. Fuks F et al DNA methyltransferase Dnmt1 associates with histone deacetylase activity. Nature Genetics 24:88, 2000 PMID: 10615135
  4. Rhee I et al CpG methylation is maintained in human cancer cells lacking DNMT1. Nature 404:1003, 2000 PMID: 10801130

Component-of

nucleolar remodeling complex (NoRC complex)