Dnmt1

DNA (cytosine-5-)-methyltransferase 1

Available structures

Ortholog search: PDBe, RCSB

List of PDB id codes
3EPZ, 3PTA, 3SWR

Identifiers

Symbols

DNMT1; AIM; CXXC9; DNMT; HSN1E; MCMT

External IDs

OMIM: 126375 MGI: 94912 HomoloGene: 124344 ChEMBL: 1993 GeneCards: DNMT1 Gene

EC number

2.1.1.37

Gene Ontology
Molecular function	• DNA binding • DNA (cytosine-5-)-methyltransferase activity • protein binding • transcription factor binding • zinc ion binding • DNA-methyltransferase activity • transferase activity • metal ion binding
Cellular component	• nucleus • replication fork • centromeric heterochromatin
Biological process	• negative regulation of transcription from RNA polymerase II promoter • DNA methylation • maintenance of DNA methylation • positive regulation of gene expression • gene silencing • chromatin modification • regulation of cell proliferation • positive regulation of histone H3-K4 methylation • negative regulation of histone H3-K9 methylation • cellular response to amino acid stimulus • C-5 methylation of cytosine
Sources: Amigo / QuickGO

RNA expression pattern

More reference expression data

Orthologs

Species

Human

Mouse

RefSeq (mRNA)

RefSeq (protein)

Location (UCSC)

Chr 19:
10.24 – 10.31 Mb

Chr 9:
20.71 – 20.76 Mb

PubMed search

[1]

[2]

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

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.^[2]^[3]

1 See also
2 Interactions
3 References
4 Further reading
5 External links

Interactions [link]

DNMT1 has been shown to interact with Histone deacetylase 2,^[4] DMAP1,^[4] PCNA,^[4]^[5]^[6] Retinoblastoma protein,^[7] DNMT3A^[8] and DNMT3B.^[8]^[9]

References [link]

^ 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. //www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=312343.
^ 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 (2011-05-01). "Mutations in DNMT1 cause hereditary sensory neuropathy with dementia and hearing loss". Nature Genetics 43 (6): 595–600. DOI:10.1038/ng.830. PMC 3102765. PMID 21532572. //www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3102765.
^ "Entrez Gene: DNMT1 DNA (cytosine-5-)-methyltransferase 1". https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=1786.
^ ^a ^b ^c Rountree, M R; Bachman K E, Baylin S B (July 2000). "DNMT1 binds HDAC2 and a new co-repressor, DMAP1, to form a complex at replication foci". Nat. Genet. (United States) 25 (3): 269–77. DOI:10.1038/77023. ISSN 1061-4036. PMID 10888872.
^ Iida, Tetsuo; Suetake Isao, Tajima Shoji, Morioka Hiroshi, Ohta Satoshi, Obuse Chikashi, Tsurimoto Toshiki (October 2002). "PCNA clamp facilitates action of DNA cytosine methyltransferase 1 on hemimethylated DNA". Genes Cells (England) 7 (10): 997–1007. DOI:10.1046/j.1365-2443.2002.00584.x. ISSN 1356-9597. PMID 12354094.
^ Chuang, L S; Ian H I, Koh T W, Ng H H, Xu G, Li B F (September 1997). "Human DNA-(cytosine-5) methyltransferase-PCNA complex as a target for p21WAF1". Science (United States) 277 (5334): 1996–2000. DOI:10.1126/science.277.5334.1996. ISSN 0036-8075. PMID 9302295.
^ Robertson, K D; Ait-Si-Ali S, Yokochi T, Wade P A, Jones P L, Wolffe A P (July 2000). "DNMT1 forms a complex with Rb, E2F1 and HDAC1 and represses transcription from E2F-responsive promoters". Nat. Genet. (United States) 25 (3): 338–42. DOI:10.1038/77124. ISSN 1061-4036. PMID 10888886.
^ ^a ^b Kim, Gun-Do; Ni Jingwei, Kelesoglu Nicole, Roberts Richard J, Pradhan Sriharsa (August 2002). "Co-operation and communication between the human maintenance and de novo DNA (cytosine-5) methyltransferases". EMBO J. (England) 21 (15): 4183–95. DOI:10.1093/emboj/cdf401. ISSN 0261-4189. PMC 126147. PMID 12145218. //www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=126147.
^ Lehnertz, Bernhard; Ueda Yoshihide, Derijck Alwin A H A, Braunschweig Ulrich, Perez-Burgos Laura, Kubicek Stefan, Chen Taiping, Li En, Jenuwein Thomas, Peters Antoine H F M (July 2003). "Suv39h-mediated histone H3 lysine 9 methylation directs DNA methylation to major satellite repeats at pericentric heterochromatin". Curr. Biol. (England) 13 (14): 1192–200. DOI:10.1016/S0960-9822(03)00432-9. ISSN 0960-9822. PMID 12867029.

Further reading [link]

Smith SS, Kaplan BE, Sowers LC, and Newman EM (1992). "Mechanism of human methyl-directed DNA methyltransferase and the fidelity of cytosine methylation". Proceedings of the National Academy of Science, U.S.A. 89 (10): 4748–4744. PMC 49160. PMID 1584813. //www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=49160.
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, et al. (1995). "E2F-5, a new E2F family member that interacts with p130 in vivo". Mol. Cell. Biol. 15 (6): 3082–9. PMC 230539. PMID 7760804. //www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=230539.
Yoder JA, Yen RW, Vertino PM, et al. (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, et al. (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, Layoon A, and 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, et al. (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. //www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=148793.
Michaelson JS, Bader D, Kuo F, et al. (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. //www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=316925.
Hsu DW, Lin MJ, Lee TL, et al. (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. //www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=22282.
Fuks F, Burgers WA, Brehm A, et al. (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, et al. (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, et al. (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, et al. (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, et al. (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. //www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=125847.
Rhee I, Bachman KE, Park BH, et al. (2002). "DNMT1 and DNMT3b cooperate to silence genes in human cancer cells". Nature 416 (6880): 552–6. DOI:10.1038/416552a. PMID 11932749.
Jair K-W, Bachman KE, Suzuki H, Ting AH, Rhee I, Yen R-WC, Baylin SB and 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 K-W, Schuebel KE, and 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 | https://www.bolnicarab.hr/upload/Svedruzic/referenca%204.pdf". Curr. Med. Chem. 15 (1): 92–106. DOI:10.2174/092986708783330700. PMID 18220765. https://www.bolnicarab.hr/upload/Svedruzic/referenca%204.pdf.
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.