DNMT1

DNA (cytosine-5-)-methyltransferase 1
Identifiers
Symbols	DNMT1; AIM; CXXC9; DNMT; FLJ16293; MCMT; MGC104992
External IDs	OMIM: 126375 MGI: 94912 HomoloGene: 124344 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 • C-5 methylation of cytosine Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	1786	13433
Ensembl	ENSG00000130816	ENSMUSG00000004099
UniProt	P26358	Q0VDW2
RefSeq (mRNA)	NM_001130823.1	NM_010066
RefSeq (protein)	NP_001124295.1	NP_034196
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]}

See also

• DNA methyltransferase

Interactions

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

References

1. ^ Yen RW, Vertino PM, Nelkin BD, Yu JJ, el-Deiry W, Cumaraswamy A, Lennon GG, Trask BJ, Celano P, Baylin SB (Jun 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. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=312343. 
2. ^ 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 May 1). "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. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3102765. 
3. ^ "Entrez Gene: DNMT1 DNA (cytosine-5-)-methyltransferase 1". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=1786. 
4. ^ ^{a b c} Rountree, M R; Bachman K E, Baylin S B (Jul. 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. 
5. ^ Iida, Tetsuo; Suetake Isao, Tajima Shoji, Morioka Hiroshi, Ohta Satoshi, Obuse Chikashi, Tsurimoto Toshiki (Oct. 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. 
6. ^ Chuang, L S; Ian H I, Koh T W, Ng H H, Xu G, Li B F (Sep. 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. 
7. ^ Robertson, K D; Ait-Si-Ali S, Yokochi T, Wade P A, Jones P L, Wolffe A P (Jul. 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. 
8. ^ ^{a b} Kim, Gun-Do; Ni Jingwei, Kelesoglu Nicole, Roberts Richard J, Pradhan Sriharsa (Aug. 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. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=126147. 
9. ^ 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 (Jul. 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

• 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. http://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. http://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. http://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. http://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. http://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. http://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 | http://www.bolnicarab.hr/upload/Svedruzic/referenca%204.pdf". Curr. Med. Chem. 15 (1): 92–106. doi:10.2174/092986708783330700. PMID 18220765. http://www.bolnicarab.hr/upload/Svedruzic/referenca%204.pdf.