DNMT1

DNMT1
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 4YOC, 3EPZ, 3PTA, 3SWR, 4WXX
Identifiers
Aliases	DNMT1, ADCADN, AIM, CXXC9, DNMT, HSN1E, MCMT, m.HsaI, DNA (cytosine-5-)-methyltransferase 1, DNA methyltransferase 1
External IDs	OMIM: 126375; MGI: 94912; HomoloGene: 124071; GeneCards: DNMT1; OMA:DNMT1 - orthologs
Gene location (Human) Chr. Chromosome 19 (human)[1] Band 19p13.2 Start 10,133,342 bp[1] End 10,231,286 bp[1]
Gene location (Mouse) Chr. Chromosome 9 (mouse)[2] Band 9 A3|9 7.66 cM Start 20,818,505 bp[2] End 20,871,184 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in oocyte secondary oocyte sural nerve ventricular zone ganglionic eminence bone marrow cells appendix cerebellar hemisphere right hemisphere of cerebellum Achilles tendon Top expressed in primary oocyte tail of embryo genital tubercle secondary oocyte zygote urethra paramesonephric duct Paneth cell somite tibiofemoral joint More reference expression data BioGPS More reference expression data
Gene ontology Molecular function methyltransferase activity DNA binding transferase activity promoter-specific chromatin binding methyl-CpG binding zinc ion binding DNA-methyltransferase activity chromatin binding metal ion binding protein binding RNA binding DNA (cytosine-5-)-methyltransferase activity DNA-binding transcription factor activity, RNA polymerase II-specific Cellular component pericentric heterochromatin replication fork nucleoplasm heterochromatin nucleus Biological process C-5 methylation of cytosine regulation of transcription, DNA-templated maintenance of DNA methylation positive regulation of DNA methylation-dependent heterochromatin assembly negative regulation of transcription by RNA polymerase II transcription, DNA-templated methylation DNA methylation positive regulation of gene expression negative regulation of gene expression, epigenetic positive regulation of histone H3-K4 methylation regulation of cell population proliferation negative regulation of histone H3-K9 methylation cellular response to amino acid stimulus regulation of gene expression Ras protein signal transduction negative regulation of transcription, DNA-templated DNA methylation on cytosine DNA methylation involved in embryo development chromatin organization DNA methylation on cytosine within a CG sequence negative regulation of gene expression positive regulation of vascular associated smooth muscle cell proliferation negative regulation of vascular associated smooth muscle cell apoptotic process negative regulation of vascular associated smooth muscle cell differentiation involved in phenotypic switching Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 1786 13433 Ensembl ENSG00000130816 ENSMUSG00000004099 UniProt P26358 P13864 RefSeq (mRNA) NM_001130823 NM_001379 NM_001318730 NM_001318731 NM_001199431 NM_001199432 NM_001199433 NM_010066 NM_001314011 RefSeq (protein) NP_001124295 NP_001305659 NP_001305660 NP_001370 NP_001186360 NP_001186361 NP_001186362 NP_001300940 NP_034196 NP_001391614 Location (UCSC) Chr 19: 10.13 – 10.23 Mb Chr 9: 20.82 – 20.87 Mb PubMed search [3] [4]
Wikidata
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DNA (cytosine-5)-methyltransferase 1 (Dnmt1) is an enzyme that catalyzes the transfer of methyl groups to specific CpG sites in DNA, a process called DNA methylation. In humans, it is encoded by the DNMT1 gene.^[5] Dnmt1 forms part of the family of DNA methyltransferase enzymes, which consists primarily of DNMT1, DNMT3A, and DNMT3B.

This enzyme is responsible for maintaining DNA methylation, which ensures the fidelity of this epigenetic patterns across cell divisions. In line with this role, it has a strong preference towards methylating CpGs on hemimethylated DNA.^[6] However, DNMT1 can catalyze de novo DNA methylation in specific genomic contexts, including transposable elements and paternal imprint control regions.^[7][8] Aberrant methylation patterns are associated with certain human tumors and developmental abnormalities.^[9][10]

• DNA methyltransferase

DNMT1 has been shown to interact with UHRF1,:

• DMAP1,^[11]
• DNMT3A^[12]
• DNMT3B,^[12][13]
• HDAC2,^[11]
• PCNA,^[11][14][15]
• RB1.^[16] and
• G9A^[17]

DNMT1 is highly transcribed during the S phase of the cell cycle when it is required for methylation of the newly generated hemimethylated sites on daughter DNA strands.^[18] Its interaction with PCNA and UHRF1 has been implicated in localizing it to the replication fork.^[19] The direct co-operation between DNMT1 and G9a coordinates DNA and H3K9 methylation during cell division.^[17] This chromatin methylation is necessary for stable repression of gene expression during mammalian development.

Knockout experiments have shown that this enzyme is responsible for the bulk of methylation in mouse cells, and it is essential for embryonic development.^[20] It has also been shown that a lack of both maternal and zygotic Dnmt1 results in complete demethylation of imprinted genes in blastocysts.^[21]

DNMT1 plays a critical role in Hematopoietic stem cell (HSC) maintenance. HSCs with reduced DNMT1 fail to self-renew efficiently post-transplantation.^[22] It has also been shown to be critical for other stem cell types such as Intestinal stem cells (ISCs) and Mammary stem cells (MaSCs). Conditional deletion of DNMT1 results in overall intestinal hypomethylation, crypt expansion and altered differentiation timing of ISCs, and proliferation and maintenance of MaSCs.^[23]

• GeneReviews/NCBI/NIH/UW entry on DNMT1-Related Dementia, Deafness, and Sensory Neuropathy