TISIDB

Summary
Symbol	DNMT1
Name	DNA (cytosine-5-)-methyltransferase 1
Aliases	MCMT; CXXC9; DNMT; ADCADN; HSN1E; CXXC-type zinc finger protein 9; DNA MTase HsaI; DNA methyltransferase Hsa ......
Chromosomal Location	19p13.2
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 [ TOP ]
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 [ TOP ]
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 [ TOP ]
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
Symbol	DNMT1
Name	DNA (cytosine-5-)-methyltransferase 1
Aliases	MCMT; CXXC9; DNMT; ADCADN; HSN1E; CXXC-type zinc finger protein 9; DNA MTase HsaI; DNA methyltransferase Hsa ......
Chromosomal Location	19p13.2
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

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Literatures describing the relation between DNMT1 and anti-tumor immunity in human cancer.

PMID	Cancer type	Relation to immunity	Evidence sentences
26503055	Ovarian Carcinoma	Inhibit 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.
29735547	Osteosarcoma	Inhibit immunity	Here 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.
23312906	Glioma; Mesothelioma	Promote immunity	In 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
Symbol	DNMT1
Name	DNA (cytosine-5-)-methyltransferase 1
Aliases	MCMT; CXXC9; DNMT; ADCADN; HSN1E; CXXC-type zinc finger protein 9; DNA MTase HsaI; DNA methyltransferase Hsa ......
Chromosomal Location	19p13.2
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

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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
29301958	CRISPR-Cas9	melanoma	B16F10	Pmel-1 T cell	NA/NS	NA/NS
29301958	CRISPR-Cas9	melanoma	B16F10	OT-1 T cell	NA/NS	NA/NS
28783722	CRISPR-Cas9	melanoma	Mel624	2CT-CRISPR	NA/NS	NA/NS
28723893	CRISPR-Cas9	melanoma	B16	GVAX+Anti-PD1	NA/NS	NA/NS
28723893	CRISPR-Cas9	melanoma	B16	GVAX	NA/NS	NA/NS
25691366	RNAi	Breast cancer	MCF7	Luc-CTL assay	NA/NS	NA/NS
24476824	shRNA	melanoma	B16	Primary screen	NA/NS	NA/NS
24476824	shRNA	melanoma	B16	Secondary screen	NA/NS	NA/NS

Summary
Symbol	DNMT1
Name	DNA (cytosine-5-)-methyltransferase 1
Aliases	MCMT; CXXC9; DNMT; ADCADN; HSN1E; CXXC-type zinc finger protein 9; DNA MTase HsaI; DNA methyltransferase Hsa ......
Chromosomal Location	19p13.2
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

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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
1	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	14	12	-0.346	0.137
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	-0.268	0.894
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	-0.405	0.788
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	0.551	0.109
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	0.267	0.919
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0.916	0.794
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	0.148	0.692
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	0.001	1
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	0.372	0.843
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	0.752	0.579
11	29301960	Clear cell renal cell carcinoma (ccRCC)	VEGFRi	Anti-PD-1 (nivolumab)	2	0	0	1
12	29301960	Clear cell renal cell carcinoma (ccRCC)	non-VEGFRi	Anti-PD-1 (nivolumab)	2	8	0.913	0.67
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	0.254	0.00167

> Mutation difference between responders and non-responders

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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
1	25765070	Non-small cell lung cancer (NSCLC)	all	Anti-PD-1 (pembrolizumab)	14	17	0	0	0	1
2	25765070	Non-small cell lung cancer (NSCLC)	smoking	Anti-PD-1 (pembrolizumab)	10	3	0	0	0	1
3	25765070	Non-small cell lung cancer (NSCLC)	non-smoking	Anti-PD-1 (pembrolizumab)	4	14	0	0	0	1
4	26359337	Melanoma	all	Anti-CTLA-4 (ipilimumab)	27	73	11.1	2.7	8.4	0.12
5	26359337	Melanoma	BRAFi	Anti-CTLA-4 (ipilimumab)	0	14	0	0	0	1
6	26359337	Melanoma	non-BRAFi	Anti-CTLA-4 (ipilimumab)	27	59	11.1	3.4	7.7	0.176
7	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	21	17	4.8	11.8	-7	0.577
8	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	6	0	0	0	1
9	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	13	11	7.7	18.2	-10.5	0.576
10	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	0	0	0	1
11	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	0	0	0	1
12	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0	0	0	1
13	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	38	27	2.6	3.7	-1.1	1
14	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	22	13	4.5	7.7	-3.2	1
15	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	16	14	0	0	0	1
16	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	11	13	0	0	0	1
17	29301960	Clear cell renal cell carcinoma (ccRCC)	VEGFRi	Anti-PD-1 (nivolumab)	6	1	0	0	0	1
18	29301960	Clear cell renal cell carcinoma (ccRCC)	non-VEGFRi	Anti-PD-1 (nivolumab)	5	12	0	0	0	1

Summary
Symbol	DNMT1
Name	DNA (cytosine-5-)-methyltransferase 1
Aliases	MCMT; CXXC9; DNMT; ADCADN; HSN1E; CXXC-type zinc finger protein 9; DNA MTase HsaI; DNA methyltransferase Hsa ......
Chromosomal Location	19p13.2
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 [ TOP ]

Summary
Symbol	DNMT1
Name	DNA (cytosine-5-)-methyltransferase 1
Aliases	MCMT; CXXC9; DNMT; ADCADN; HSN1E; CXXC-type zinc finger protein 9; DNA MTase HsaI; DNA methyltransferase Hsa ......
Chromosomal Location	19p13.2
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 [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	DNMT1
Name	DNA (cytosine-5-)-methyltransferase 1
Aliases	MCMT; CXXC9; DNMT; ADCADN; HSN1E; CXXC-type zinc finger protein 9; DNA MTase HsaI; DNA methyltransferase Hsa ......
Chromosomal Location	19p13.2
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 [ TOP ]

> Receptor [ TOP ]

Summary
Symbol	DNMT1
Name	DNA (cytosine-5-)-methyltransferase 1
Aliases	MCMT; CXXC9; DNMT; ADCADN; HSN1E; CXXC-type zinc finger protein 9; DNA MTase HsaI; DNA methyltransferase Hsa ......
Chromosomal Location	19p13.2
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of DNMT1 expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	DNMT1
Name	DNA (cytosine-5-)-methyltransferase 1
Aliases	MCMT; CXXC9; DNMT; ADCADN; HSN1E; CXXC-type zinc finger protein 9; DNA MTase HsaI; DNA methyltransferase Hsa ......
Chromosomal Location	19p13.2
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between DNMT1 and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	DNMT1
Name	DNA (cytosine-5-)-methyltransferase 1
Aliases	MCMT; CXXC9; DNMT; ADCADN; HSN1E; CXXC-type zinc finger protein 9; DNA MTase HsaI; DNA methyltransferase Hsa ......
Chromosomal Location	19p13.2
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting DNMT1 collected from DrugBank database.

> Drugs from DrugBank database

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Details on drugs targeting DNMT1.

ID	Name	Drug Type	Targets	#Targets
DB00928	Azacitidine	Small Molecule	DNMT1	1
DB01035	Procainamide	Small Molecule	DNMT1, KCNH2, SCN5A	3
DB01099	Flucytosine	Small Molecule	DNMT1	1
DB01262	Decitabine	Small Molecule	DNMT1	1
DB05668	Palifosfamide	Small Molecule	DNMT1	1
DB12116	Epigallocatechin Gallate	Small Molecule	AHR, DHFRL1, DNMT1	3

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