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
Gene location (Human)
Chr.	Chromosome 19 (human)
End	10,231,286 bp
Gene location (Mouse)
Chr.	Chromosome 9 (mouse)
End	20,871,184 bp
RNA expression pattern
	Top expressed in
	oocyte; ; secondary oocyte; ; sural nerve; ; ganglionic eminence; ; bone marrow cells; ; appendix; ; cerebellar hemisphere; ; Achilles tendon; ; lymph node; ; placenta;
	Top expressed in
	secondary oocyte; ; urethra; ; Paneth cell; ; somite; ; renal corpuscle; ; condyle; ; maxillary prominence; ; epithelium of urethra; ; medullary collecting duct; ; cumulus cell;
	More reference expression data
	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
	1786
	13433
	ENSG00000130816
	ENSMUSG00000004099
	P26358
	P13864
	NM_001130823; NM_001379; NM_001318730; NM_001318731
	NM_001199431; NM_001199432; NM_001199433; NM_010066; NM_001314011
	NP_001124295; NP_001305659; NP_001305660; NP_001370
NP_001186360; NP_001186361; NP_001186362; NP_001300940; NP_034196;
	NP_001391614
	Wikidata
View/Edit Human	View/Edit Mouse

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

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.^[6]^[7]

Interactions

DNMT1 has been shown to interact with UHRF1,:

References

^ ^a ^b ^c GRCh38: Ensembl release 89: ENSG00000130816 – Ensembl, May 2017
^ ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000004099 – Ensembl, May 2017
^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ 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".
^ ^a ^b ^c 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.
^ ^a ^b 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.{{cite journal}}: CS1 maint: unflagged free DOI (link)
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.{{cite journal}}: CS1 maint: unflagged free DOI (link)
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.{{cite journal}}: CS1 maint: unflagged free DOI (link)
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. {{cite journal}}: 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

[refGRCh38Ensembl-1] GRCh38: Ensembl release 89: ENSG00000130816 – Ensembl, May 2017

[refGRCm38Ensembl-2] GRCm38: Ensembl release 89: ENSMUSG00000004099 – Ensembl, May 2017

[3] "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[4] "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[pmid1594447-5] 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.

[pmid21532572-6] 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.

[7] "Entrez Gene: DNMT1 DNA (cytosine-5-)-methyltransferase 1".

[pmid10888872-8] 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.

[pmid12145218-9] 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.

[pmid12867029-10] 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.

[pmid12354094-11] 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.

[pmid9302295-12] 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.

[pmid10888886-13] 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.

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DNMT1

Function

See also

Interactions

References

Further reading

External links