DNMT1

Available structures

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

External IDs

OMIM: 126375 MGI: 94912 HomoloGene: 124071 GeneCards: DNMT1

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
Cellular component	• pericentric heterochromatin • replication fork • nucleoplasm • heterochromatin • nucleus
Biological process	• gene silencing • C-5 methylation of cytosine • regulation of transcription, DNA-templated • maintenance of DNA methylation • positive regulation of methylation-dependent chromatin silencing • negative regulation of transcription from RNA polymerase II promoter • 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 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 • covalent chromatin modification
Sources:Amigo / QuickGO

RNA expression pattern

More reference expression data

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_001124295.1 NP_001370.1 NP_001305659.1 NP_001305660.1


NP_001186360.2 NP_001186361.1 NP_001186362.1 NP_034196.5 NP_001300940.1

Location (UCSC)

Chr 19: 10.13 – 10.23 Mb

Chr 9: 20.91 – 20.96 Mb

PubMed search

^[1]

^[2]

Wikidata

View/Edit Human

View/Edit Mouse

DNA (cytosine-5)-methyltransferase 1 is an enzyme that in humans is encoded by the DNMT1 gene.^[3]

Function

DNA (cytosine-5-)-methyltransferase 1 has a role in the establishment and regulation of tissue-specific patterns of methylated cytosine residues. Aberrant methylation patterns are associated with certain human tumors and developmental abnormalities.^[4]^[5]

Interactions

DNMT1 has been shown to interact with UHRF1,:

References

↑ "Human PubMed Reference:".
↑ "Mouse PubMed Reference:".
↑ Yen RW, Vertino PM, Nelkin BD, Yu JJ, el-Deiry W, Cumaraswamy A, Lennon GG, Trask BJ, Celano P, Baylin SB (June 1992). "Isolation and characterization of the cDNA encoding human DNA methyltransferase". Nucleic Acids Res. 20 (9): 2287–91. doi:10.1093/nar/20.9.2287. PMC 312343. PMID 1594447.
↑ Klein CJ, Botuyan MV, Wu Y, Ward CJ, Nicholson GA, Hammans S, Hojo K, Yamanishi H, Karpf AR, Wallace DC, Simon M, Lander C, Boardman LA, Cunningham JM, Smith GE, Litchy WJ, Boes B, Atkinson EJ, Middha S, B Dyck PJ, Parisi JE, Mer G, Smith DI, Dyck PJ (2011). "Mutations in DNMT1 cause hereditary sensory neuropathy with dementia and hearing loss". Nat. Genet. 43 (6): 595–600. doi:10.1038/ng.830. PMC 3102765. PMID 21532572.
↑ "Entrez Gene: DNMT1 DNA (cytosine-5-)-methyltransferase 1".
1 2 3 Rountree MR, Bachman KE, Baylin SB (July 2000). "DNMT1 binds HDAC2 and a new co-repressor, DMAP1, to form a complex at replication foci". Nat. Genet. 25 (3): 269–77. doi:10.1038/77023. PMID 10888872.
1 2 Kim GD, Ni J, Kelesoglu N, Roberts RJ, Pradhan S (August 2002). "Co-operation and communication between the human maintenance and de novo DNA (cytosine-5) methyltransferases". EMBO J. 21 (15): 4183–95. doi:10.1093/emboj/cdf401. PMC 126147. PMID 12145218.
↑ Lehnertz B, Ueda Y, Derijck AA, Braunschweig U, Perez-Burgos L, Kubicek S, Chen T, Li E, Jenuwein T, Peters AH (July 2003). "Suv39h-mediated histone H3 lysine 9 methylation directs DNA methylation to major satellite repeats at pericentric heterochromatin". Curr. Biol. 13 (14): 1192–200. doi:10.1016/s0960-9822(03)00432-9. PMID 12867029.
↑ Iida T, Suetake I, Tajima S, Morioka H, Ohta S, Obuse C, Tsurimoto T (October 2002). "PCNA clamp facilitates action of DNA cytosine methyltransferase 1 on hemimethylated DNA". Genes Cells. 7 (10): 997–1007. doi:10.1046/j.1365-2443.2002.00584.x. PMID 12354094.
↑ Chuang LS, Ian HI, Koh TW, Ng HH, Xu G, Li BF (September 1997). "Human DNA-(cytosine-5) methyltransferase-PCNA complex as a target for p21WAF1". Science. 277 (5334): 1996–2000. doi:10.1126/science.277.5334.1996. PMID 9302295.
↑ Robertson KD, Ait-Si-Ali S, Yokochi T, Wade PA, Jones PL, Wolffe AP (July 2000). "DNMT1 forms a complex with Rb, E2F1 and HDAC1 and represses transcription from E2F-responsive promoters". Nat. Genet. 25 (3): 338–42. doi:10.1038/77124. PMID 10888886.

Smith SS, Kaplan BE, Sowers LC, Newman EM (1992). "Mechanism of human methyl-directed DNA methyltransferase and the fidelity of cytosine methylation". Proceedings of the National Academy of Sciences of the United States of America. 89 (10): 4748–4744. doi:10.1073/pnas.89.10.4744. PMC 49160. PMID 1584813.
Bestor T, Laudano A, Mattaliano R, Ingram V (1989). "Cloning and sequencing of a cDNA encoding DNA methyltransferase of mouse cells. The carboxyl-terminal domain of the mammalian enzymes is related to bacterial restriction methyltransferases". J. Mol. Biol. 203 (4): 971–83. doi:10.1016/0022-2836(88)90122-2. PMID 3210246.
Smith SS (1994). "Mechanism of Human Methyl-directed DNA methyltransferase and the Fidelity of Cytosine Methylation". Progress in Nucleic Acids Research and Molecular Biology. 49: 65–111. PMID 7863011.
Hijmans EM, Voorhoeve PM, Beijersbergen RL, van 't Veer LJ, Bernards R (1995). "E2F-5, a new E2F family member that interacts with p130 in vivo". Mol. Cell. Biol. 15 (6): 3082–9. doi:10.1128/mcb.15.6.3082. PMC 230539. PMID 7760804.
Yoder JA, Yen RW, Vertino PM, Bestor TH, Baylin SB (1997). "New 5' regions of the murine and human genes for DNA (cytosine-5)-methyltransferase". J. Biol. Chem. 271 (49): 31092–7. doi:10.1074/jbc.271.49.31092. PMID 8940105.
Chuang LS, Ian HI, Koh TW, Ng HH, Xu G, Li BF (1997). "Human DNA-(cytosine-5) methyltransferase-PCNA complex as a target for p21WAF1". Science. 277 (5334): 1996–2000. doi:10.1126/science.277.5334.1996. PMID 9302295.
Kho MR, Baker DJ, Laayoun A, Smith SS (1998). "Stalling of Human DNA (Cytosine-5)Methyltransferase at Single Strand Conformers form a Site of Dynamic Mutation". Journal of Molecular Biology. 275 (1): 67–79. doi:10.1006/jmbi.1997.1430. PMID 9451440.
Baylin SB (1997). "Tying it all together: epigenetics, genetics, cell cycle, and cancer". Science. 277 (5334): 1948–9. doi:10.1126/science.277.5334.1948. PMID 9333948.
Robertson KD, Uzvolgyi E, Liang G, Talmadge C, Sumegi J, Gonzales FA, Jones PA (1999). "The human DNA methyltransferases (DNMTs) 1, 3a and 3b: coordinate mRNA expression in normal tissues and overexpression in tumors". Nucleic Acids Res. 27 (11): 2291–8. doi:10.1093/nar/27.11.2291. PMC 148793. PMID 10325416.
Michaelson JS, Bader D, Kuo F, Kozak C, Leder P (1999). "Loss of Daxx, a promiscuously interacting protein, results in extensive apoptosis in early mouse development". Genes Dev. 13 (15): 1918–23. doi:10.1101/gad.13.15.1918. PMC 316925. PMID 10444590.
Hsu DW, Lin MJ, Lee TL, Wen SC, Chen X, Shen CK (1999). "Two major forms of DNA (cytosine-5) methyltransferase in human somatic tissues". Proc. Natl. Acad. Sci. U.S.A. 96 (17): 9751–6. doi:10.1073/pnas.96.17.9751. PMC 22282. PMID 10449766.
Fuks F, Burgers WA, Brehm A, Hughes-Davies L, Kouzarides T (2000). "DNA methyltransferase Dnmt1 associates with histone deacetylase activity". Nat. Genet. 24 (1): 88–91. doi:10.1038/71750. PMID 10615135.
Bonfils C, Beaulieu N, Chan E, Cotton-Montpetit J, MacLeod AR (2000). "Characterization of the human DNA methyltransferase splice variant Dnmt1b". J. Biol. Chem. 275 (15): 10754–60. doi:10.1074/jbc.275.15.10754. PMID 10753866.
Rountree MR, Bachman KE, Baylin SB (2000). "DNMT1 binds HDAC2 and a new co-repressor, DMAP1, to form a complex at replication foci". Nat. Genet. 25 (3): 269–77. doi:10.1038/77023. PMID 10888872.
Robertson KD, Ait-Si-Ali S, Yokochi T, Wade PA, Jones PL, Wolffe AP (2000). "DNMT1 forms a complex with Rb, E2F1 and HDAC1 and represses transcription from E2F-responsive promoters". Nat. Genet. 25 (3): 338–42. doi:10.1038/77124. PMID 10888886.
Tatematsu KI, Yamazaki T, Ishikawa F (2000). "MBD2-MBD3 complex binds to hemi-methylated DNA and forms a complex containing DNMT1 at the replication foci in late S phase". Genes Cells. 5 (8): 677–88. doi:10.1046/j.1365-2443.2000.00359.x. PMID 10947852.
Mizuno S, Chijiwa T, Okamura T, Akashi K, Fukumaki Y, Niho Y, Sasaki H (2001). "Expression of DNA methyltransferases DNMT1, 3A, and 3B in normal hematopoiesis and in acute and chronic myelogenous leukemia". Blood. 97 (5): 1172–9. doi:10.1182/blood.V97.5.1172. PMID 11222358.
Fatemi M, Hermann A, Pradhan S, Jeltsch A (2001). "The activity of the murine DNA methyltransferase Dnmt1 is controlled by interaction of the catalytic domain with the N-terminal part of the enzyme leading to an allosteric activation of the enzyme after binding to methylated DNA". J. Mol. Biol. 309 (5): 1189–99. doi:10.1006/jmbi.2001.4709. PMID 11399088.
Dintilhac A, Bernués J (2002). "HMGB1 interacts with many apparently unrelated proteins by recognizing short amino acid sequences". J. Biol. Chem. 277 (9): 7021–8. doi:10.1074/jbc.M108417200. PMID 11748221.
Di Croce L, Raker VA, Corsaro M, Fazi F, Fanelli M, Faretta M, Fuks F, Lo Coco F, Kouzarides T, Nervi C, Minucci S, Pelicci PG (2002). "Methyltransferase recruitment and DNA hypermethylation of target promoters by an oncogenic transcription factor". Science. 295 (5557): 1079–82. doi:10.1126/science.1065173. PMID 11834837.
Pradhan S, Kim GD (2002). "The retinoblastoma gene product interacts with maintenance human DNA (cytosine-5) methyltransferase and modulates its activity". EMBO J. 21 (4): 779–88. doi:10.1093/emboj/21.4.779. PMC 125847. PMID 11847125.
Rhee I, Bachman KE, Park BH, Jair KW, Yen RW, Schuebel KE, Cui H, Feinberg AP, Lengauer C, Kinzler KW, Baylin SB, Vogelstein B (2002). "DNMT1 and DNMT3b cooperate to silence genes in human cancer cells". Nature. 416 (6880): 552–6. doi:10.1038/416552a. PMID 11932749.
Jair KW, Bachman KE, Suzuki H, Ting AH, Rhee I, Yen RW, Baylin SB, Schuebel KE (2006). "De novo CpG Island Methylation in Human Cancer Cells". Cancer Research. 69 (2): 682–692. doi:10.1158/0008-5472.CAN-05-1980. PMID 16423997.
Ting AH, Jair KW, Schuebel KE, Baylin SB (2006). "Differential Requirement for DNA Methyltransferse 1 In Maintianing Cancer Cell Gene Promoter Hypermethylation". Cancer Research. 66 (2): 729–735. doi:10.1158/0008-5472.CAN-05-1537. PMID 16424002.
Svedruzić ZM (2008). "Mammalian cytosine DNA methyltransferase Dnmt1: enzymatic mechanism, novel mechanism-based inhibitors, and RNA-directed DNA methylation | http://www.bolnicarab.hr/upload/Svedruzic/referenca%204.pdf" (PDF). Curr. Med. Chem. 15 (1): 92–106. doi:10.2174/092986708783330700. PMID 18220765. External link in |title= (help)
Bestor T, Laudano A, Mattaliano R, Ingram V (1988). "Cloning and sequencing of a cDNA encoding DNA methyltransferase of mouse cells. The carboxyl-terminal domain of the mammalian enzymes is related to bacterial restriction methyltransferases". Journal of Molecular Biology. 203 (4): 971–983. doi:10.1016/0022-2836(88)90122-2. PMID 3210246.

External links

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

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DNMT1

Function

See also

Interactions

References

Further reading

External links