Browse DNMT1

Summary
SymbolDNMT1
NameDNA (cytosine-5-)-methyltransferase 1
Aliases MCMT; CXXC9; DNMT; ADCADN; HSN1E; CXXC-type zinc finger protein 9; DNA MTase HsaI; DNA methyltransferase Hsa ......
Chromosomal Location19p13.2
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Basic function annotation.
> Subcellular Location, Domain and Function
> Gene Ontology
> KEGG and Reactome Pathway
> Subcellular Location, Domain and Function
 
Subcellular Location Nucleus
Domain PF01426 BAH domain
PF06464 DMAP1-binding Domain
PF00145 C-5 cytosine-specific DNA methylase
PF12047 Cytosine specific DNA methyltransferase replication foci domain
PF02008 CXXC zinc finger domain
Function

Methylates CpG residues. 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 and M phases to maintain DNA methylation independently of replication. It is 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 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. Probably forms a corepressor complex required for activated KRAS-mediated promoter hypermethylation and transcriptional silencing of tumor suppressor genes (TSGs) or other tumor-related genes in colorectal cancer (CRC) cells (PubMed:24623306). Also required to maintain a transcriptionally repressive state of genes in undifferentiated embryonic stem cells (ESCs) (PubMed:24623306). Associates at promoter regions of tumor suppressor genes (TSGs) leading to their gene silencing (PubMed:24623306). Promotes tumor growth (PubMed:24623306).

> Gene Ontology
 
Biological Process GO:0001101 response to acid chemical
GO:0006304 DNA modification
GO:0006305 DNA alkylation
GO:0006306 DNA methylation
GO:0006342 chromatin silencing
GO:0006346 methylation-dependent chromatin silencing
GO:0006479 protein methylation
GO:0007265 Ras protein signal transduction
GO:0008213 protein alkylation
GO:0010216 maintenance of DNA methylation
GO:0016458 gene silencing
GO:0016570 histone modification
GO:0016571 histone methylation
GO:0018022 peptidyl-lysine methylation
GO:0018205 peptidyl-lysine modification
GO:0031056 regulation of histone modification
GO:0031057 negative regulation of histone modification
GO:0031058 positive regulation of histone modification
GO:0031060 regulation of histone methylation
GO:0031061 negative regulation of histone methylation
GO:0031062 positive regulation of histone methylation
GO:0031935 regulation of chromatin silencing
GO:0031937 positive regulation of chromatin silencing
GO:0032259 methylation
GO:0032776 DNA methylation on cytosine
GO:0034968 histone lysine methylation
GO:0040029 regulation of gene expression, epigenetic
GO:0043200 response to amino acid
GO:0043414 macromolecule methylation
GO:0044728 DNA methylation or demethylation
GO:0045814 negative regulation of gene expression, epigenetic
GO:0051052 regulation of DNA metabolic process
GO:0051054 positive regulation of DNA metabolic process
GO:0051567 histone H3-K9 methylation
GO:0051568 histone H3-K4 methylation
GO:0051569 regulation of histone H3-K4 methylation
GO:0051570 regulation of histone H3-K9 methylation
GO:0051571 positive regulation of histone H3-K4 methylation
GO:0051573 negative regulation of histone H3-K9 methylation
GO:0060968 regulation of gene silencing
GO:0061647 histone H3-K9 modification
GO:0071229 cellular response to acid chemical
GO:0071230 cellular response to amino acid stimulus
GO:0071417 cellular response to organonitrogen compound
GO:0090116 C-5 methylation of cytosine
GO:0090308 regulation of methylation-dependent chromatin silencing
GO:0090309 positive regulation of methylation-dependent chromatin silencing
GO:1902275 regulation of chromatin organization
GO:1905268 negative regulation of chromatin organization
GO:1905269 positive regulation of chromatin organization
Molecular Function GO:0003682 chromatin binding
GO:0003886 DNA (cytosine-5-)-methyltransferase activity
GO:0008168 methyltransferase activity
GO:0008327 methyl-CpG binding
GO:0008757 S-adenosylmethionine-dependent methyltransferase activity
GO:0009008 DNA-methyltransferase activity
GO:0016741 transferase activity, transferring one-carbon groups
GO:1990841 promoter-specific chromatin binding
Cellular Component GO:0000775 chromosome, centromeric region
GO:0000785 chromatin
GO:0000792 heterochromatin
GO:0005657 replication fork
GO:0005721 pericentric heterochromatin
GO:0098687 chromosomal region
> KEGG and Reactome Pathway
 
KEGG hsa00270 Cysteine and methionine metabolism
hsa01100 Metabolic pathways
Reactome R-HSA-5334118: DNA methylation
R-HSA-212165: Epigenetic regulation of gene expression
R-HSA-74160: Gene Expression
R-HSA-5250941: Negative epigenetic regulation of rRNA expression
R-HSA-427413: NoRC negatively regulates rRNA expression
R-HSA-212300: PRC2 methylates histones and DNA
Summary
SymbolDNMT1
NameDNA (cytosine-5-)-methyltransferase 1
Aliases MCMT; CXXC9; DNMT; ADCADN; HSN1E; CXXC-type zinc finger protein 9; DNA MTase HsaI; DNA methyltransferase Hsa ......
Chromosomal Location19p13.2
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Literatures that report relations between DNMT1 and anti-tumor immunity. The specific mechanism were also collected if the literature reports that a gene specifically promotes or inhibits the infiltration or function of T/NK cells.
> Text Mining
 
  Literatures describing the relation between DNMT1 and anti-tumor immunity in human cancer.
PMID Cancer type Relation to immunity Evidence sentences
26503055Ovarian CarcinomaInhibit immunity (infiltration)Using human ovarian cancers as our model, here we show that enhancer of zeste homologue 2 (EZH2)-mediated histone H3 lysine 27 trimethylation (H3K27me3) and DNA methyltransferase 1 (DNMT1)-mediated DNA methylation repress the tumour production of T helper 1 (TH1)-type chemokines CXCL9 and CXCL10, and subsequently determine effector T-cell trafficking to the tumour microenvironment.
29735547OsteosarcomaInhibit immunityHere we show for the first time that osteosarcomas epigenetically downregulate CXCL12 expression via DNA methyltransferase 1 (DNMT1) and consequently acquire the ability to metastasize and impair cytotoxic T-cell homing to the tumor site. Critically, treatment targeting DNMT1 in immunocompetent mouse models significantly elevated expression of CXCL12 in tumors, resulting in a robust immune response and consequently eradicating early lung metastases in addition to suppressing subcutaneous tumor growth.
23312906Glioma; MesotheliomaPromote immunityIn two non epithelial cancers (glioma and mesothelioma), we found that the epigenetic regulation of the NY-ESO1 gene requires the sequential recruitment of the HDAC1-mSin3a-NCOR, Dnmt3b-HDAC1-Egr1 and Dnmt1-PCNA-UHRF1-G9a complexes.The NY-ESO1 gene is a cancer/testis antigen considered to be suitable target for the immunotherapy of human malignancies.
Summary
SymbolDNMT1
NameDNA (cytosine-5-)-methyltransferase 1
Aliases MCMT; CXXC9; DNMT; ADCADN; HSN1E; CXXC-type zinc finger protein 9; DNA MTase HsaI; DNA methyltransferase Hsa ......
Chromosomal Location19p13.2
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content High-throughput screening data (e.g. CRISPR-Cas9, shRNA and RNAi) for T cell-mediated killing. Genetic screen techniques can identify mechanisms of tumor cell resistance (e.g., PTPN2) and sensitivity (e.g., APLNR) to killing by cytotoxic T cells, the central effectors of anti-tumor immunity. After comprehensively searching, eight groups of screening data sets were collected in the current database. In this tab, users can check whether their selected genes cause resistance or increase sensitivity to T cell-mediated killing in various data sets.
> High-throughput Screening
  Statistical results of DNMT1 in screening data sets for detecting immune reponses.
PMID Screening System Cancer Type Cell Line Data Set Statistical Results Relation to immunity
29301958CRISPR-Cas9 melanomaB16F10Pmel-1 T cell NA/NSNA/NS
29301958CRISPR-Cas9 melanomaB16F10OT-1 T cell NA/NSNA/NS
28783722CRISPR-Cas9 melanomaMel6242CT-CRISPR NA/NSNA/NS
28723893CRISPR-Cas9 melanomaB16GVAX+Anti-PD1 NA/NSNA/NS
28723893CRISPR-Cas9 melanomaB16GVAX NA/NSNA/NS
25691366RNAiBreast cancerMCF7Luc-CTL assay NA/NSNA/NS
24476824shRNAmelanomaB16Primary screen NA/NSNA/NS
24476824shRNAmelanomaB16Secondary screen NA/NSNA/NS
Summary
SymbolDNMT1
NameDNA (cytosine-5-)-methyltransferase 1
Aliases MCMT; CXXC9; DNMT; ADCADN; HSN1E; CXXC-type zinc finger protein 9; DNA MTase HsaI; DNA methyltransferase Hsa ......
Chromosomal Location19p13.2
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Transcriptomic and genomic profiling of pre-treated tumor biopsies from responders and non-responders to immunotherapy. These data were used to identify signatures and mechanisms of response to checkpoint blockade (e.g., anti-PDL1 and anti-PD1). One example is that mutations in the gene PBRM1 benefit clinical survival of patients with clear cell renal cell carcinoma. After comprehensively searching, we collected 5 and 6 of transcriptomic and genomic data sets, respectively. In this tab, users can check whether their selected genes have significant difference of expression or mutation between responders and non-responders in various data sets.
> Expression difference between responders and non-responders
> Mutation difference between responders and non-responders
> Expression difference between responders and non-responders
 
Points in the above scatter plot represent the expression difference of DNMT1 in various data sets.
No PMID Cancer type Group Drug # Res # NRes Log2 (Fold Change) P value Anno
126997480MelanomaallAnti-PD-1 (pembrolizumab and nivolumab)1412-0.3460.137
226997480MelanomaMAPKiAnti-PD-1 (pembrolizumab and nivolumab)65-0.2680.894
326997480Melanomanon-MAPKiAnti-PD-1 (pembrolizumab and nivolumab)87-0.4050.788
428552987Urothelial cancerallAnti-PD-L1 (atezolizumab) 9160.5510.109
528552987Urothelial cancersmokingAnti-PD-L1 (atezolizumab) 590.2670.919
628552987Urothelial cancernon-smokingAnti-PD-L1 (atezolizumab) 470.9160.794
729033130MelanomaallAnti-PD-1 (nivolumab) 26230.1480.692
829033130MelanomaNIV3-PROGAnti-PD-1 (nivolumab) 15110.0011
929033130MelanomaNIV3-NAIVEAnti-PD-1 (nivolumab) 11120.3720.843
1029301960Clear cell renal cell carcinoma (ccRCC)allAnti-PD-1 (nivolumab) 480.7520.579
1129301960Clear cell renal cell carcinoma (ccRCC)VEGFRiAnti-PD-1 (nivolumab) 2001
1229301960Clear cell renal cell carcinoma (ccRCC)non-VEGFRiAnti-PD-1 (nivolumab) 280.9130.67
1329443960Urothelial cancerallAnti-PD-L1 (atezolizumab) 682300.2540.00167
> Mutation difference between responders and non-responders
 
Points in the above scatter plot represent the mutation difference of DNMT1 in various data sets.
No PMID Cancer type Group Drug # Res # NRes % Mut/Res % Mut/NRes % Diff (R vs NR) Pval Anno
125765070Non-small cell lung cancer (NSCLC)allAnti-PD-1 (pembrolizumab) 14170001
225765070Non-small cell lung cancer (NSCLC)smokingAnti-PD-1 (pembrolizumab) 1030001
325765070Non-small cell lung cancer (NSCLC)non-smokingAnti-PD-1 (pembrolizumab) 4140001
426359337MelanomaallAnti-CTLA-4 (ipilimumab) 277311.12.78.40.12
526359337MelanomaBRAFiAnti-CTLA-4 (ipilimumab) 0140001
626359337Melanomanon-BRAFiAnti-CTLA-4 (ipilimumab) 275911.13.47.70.176
726997480MelanomaallAnti-PD-1 (pembrolizumab and nivolumab)21174.811.8-70.577
826997480MelanomaMAPKiAnti-PD-1 (pembrolizumab and nivolumab)860001
926997480Melanomanon-MAPKiAnti-PD-1 (pembrolizumab and nivolumab)13117.718.2-10.50.576
1028552987Urothelial cancerallAnti-PD-L1 (atezolizumab) 9160001
1128552987Urothelial cancersmokingAnti-PD-L1 (atezolizumab) 590001
1228552987Urothelial cancernon-smokingAnti-PD-L1 (atezolizumab) 470001
1329033130MelanomaallAnti-PD-1 (nivolumab) 38272.63.7-1.11
1429033130MelanomaNIV3-PROGAnti-PD-1 (nivolumab) 22134.57.7-3.21
1529033130MelanomaNIV3-NAIVEAnti-PD-1 (nivolumab) 16140001
1629301960Clear cell renal cell carcinoma (ccRCC)allAnti-PD-1 (nivolumab) 11130001
1729301960Clear cell renal cell carcinoma (ccRCC)VEGFRiAnti-PD-1 (nivolumab) 610001
1829301960Clear cell renal cell carcinoma (ccRCC)non-VEGFRiAnti-PD-1 (nivolumab) 5120001
Summary
SymbolDNMT1
NameDNA (cytosine-5-)-methyltransferase 1
Aliases MCMT; CXXC9; DNMT; ADCADN; HSN1E; CXXC-type zinc finger protein 9; DNA MTase HsaI; DNA methyltransferase Hsa ......
Chromosomal Location19p13.2
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of DNMT1. The immune-related signatures of 28 TIL types from Charoentong's study, which can be viewed in the download page. For each cancer type, the relative abundance of TILs were inferred by using gene set variation analysis (GSVA) based on gene expression profile. In this tab, users can examine which kinds of TILs might be regulated by the current gene.
> Lymphocyte
 
Summary
SymbolDNMT1
NameDNA (cytosine-5-)-methyltransferase 1
Aliases MCMT; CXXC9; DNMT; ADCADN; HSN1E; CXXC-type zinc finger protein 9; DNA MTase HsaI; DNA methyltransferase Hsa ......
Chromosomal Location19p13.2
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of DNMT1. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by DNMT1.
> Immunoinhibitor
> Immunostimulator
> MHC molecule
> Immunoinhibitor
 
> Immunostimulator
 
> MHC molecule
 
Summary
SymbolDNMT1
NameDNA (cytosine-5-)-methyltransferase 1
Aliases MCMT; CXXC9; DNMT; ADCADN; HSN1E; CXXC-type zinc finger protein 9; DNA MTase HsaI; DNA methyltransferase Hsa ......
Chromosomal Location19p13.2
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of DNMT1. In this tab, users can examine which chemokines (or receptors) might be regulated by the current gene.
> Chemokine
> Receptor
> Chemokine
 
> Receptor
 
Summary
SymbolDNMT1
NameDNA (cytosine-5-)-methyltransferase 1
Aliases MCMT; CXXC9; DNMT; ADCADN; HSN1E; CXXC-type zinc finger protein 9; DNA MTase HsaI; DNA methyltransferase Hsa ......
Chromosomal Location19p13.2
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Distribution of DNMT1 expression across immune and molecular subtypes.
> Immune subtype
> Molecular subtype
> Immune subtype
 
> Molecular subtype
 
Summary
SymbolDNMT1
NameDNA (cytosine-5-)-methyltransferase 1
Aliases MCMT; CXXC9; DNMT; ADCADN; HSN1E; CXXC-type zinc finger protein 9; DNA MTase HsaI; DNA methyltransferase Hsa ......
Chromosomal Location19p13.2
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Associations between DNMT1 and clinical features.
> Overall survival analysis
> Cancer stage
> Tumor grade
> Overall survival
 
> Stage
 
> Grade
 
Summary
SymbolDNMT1
NameDNA (cytosine-5-)-methyltransferase 1
Aliases MCMT; CXXC9; DNMT; ADCADN; HSN1E; CXXC-type zinc finger protein 9; DNA MTase HsaI; DNA methyltransferase Hsa ......
Chromosomal Location19p13.2
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Drugs targeting DNMT1 collected from DrugBank database.
> Drugs from DrugBank database
 

  Details on drugs targeting DNMT1.
ID Name Drug Type Targets #Targets
DB00928AzacitidineSmall MoleculeDNMT11
DB01035ProcainamideSmall MoleculeDNMT1, KCNH2, SCN5A3
DB01099FlucytosineSmall MoleculeDNMT11
DB01262DecitabineSmall MoleculeDNMT11
DB05668PalifosfamideSmall MoleculeDNMT11
DB12116Epigallocatechin GallateSmall MoleculeAHR, DHFRL1, DNMT13