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{{Infobox_gene}}
{{PBB_Controls
'''DNA (cytosine-5)-methyltransferase 1''' is an [[enzyme]] that catalyzes the transfer of methyl groups to specific CpG structures in DNA, a process called [[DNA methylation]]. In humans, it is encoded by the ''DNMT1'' [[gene]].<ref name="pmid1594447">{{cite journal | vauthors = Yen RW, Vertino PM, Nelkin BD, Yu JJ, el-Deiry W, Cumaraswamy A, Lennon GG, Trask BJ, Celano P, Baylin SB | title = Isolation and characterization of the cDNA encoding human DNA methyltransferase | journal = Nucleic Acids Research | volume = 20 | issue = 9 | pages = 2287–91 | date = May 1992 | pmid = 1594447 | pmc = 312343 | doi = 10.1093/nar/20.9.2287 }}</ref> DNMT1 forms part of the family of [[DNA methyltransferase]] enzymes, which consists primarily of DNMT1, [[DNA (cytosine-5)-methyltransferase 3A|DNMT3A]], and [[DNMT3B]].
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<!-- The GNF_Protein_box is automatically maintained by Protein Box Bot.  See Template:PBB_Controls to Stop updates. -->
== Function ==
{{GNF_Protein_box
| image =
| image_source =
| PDB =
| Name = DNA (cytosine-5-)-methyltransferase 1
| HGNCid = 2976
| Symbol = DNMT1
| AltSymbols =; CXXC9; DNMT; FLJ16293; MCMT; MGC104992
| OMIM = 126375
| ECnumber = 
| Homologene = 1055
| MGIid = 94912
| GeneAtlas_image1 = PBB_GE_DNMT1_201697_s_at_tn.png
| Function = {{GNF_GO|id=GO:0003677 |text = DNA binding}} {{GNF_GO|id=GO:0003886 |text = DNA (cytosine-5-)-methyltransferase activity}} {{GNF_GO|id=GO:0008134 |text = transcription factor binding}} {{GNF_GO|id=GO:0008168 |text = methyltransferase activity}} {{GNF_GO|id=GO:0008270 |text = zinc ion binding}} {{GNF_GO|id=GO:0016740 |text = transferase activity}} {{GNF_GO|id=GO:0046872 |text = metal ion binding}}
| Component = {{GNF_GO|id=GO:0005634 |text = nucleus}}
| Process = {{GNF_GO|id=GO:0000122 |text = negative regulation of transcription from RNA polymerase II promoter}} {{GNF_GO|id=GO:0006306 |text = DNA methylation}} {{GNF_GO|id=GO:0006350 |text = transcription}} {{GNF_GO|id=GO:0006355 |text = regulation of transcription, DNA-dependent}}
| Orthologs = {{GNF_Ortholog_box
    | Hs_EntrezGene = 1786
    | Hs_Ensembl = ENSG00000130816
    | Hs_RefseqProtein = NP_001370
    | Hs_RefseqmRNA = NM_001379
    | Hs_GenLoc_db = 
    | Hs_GenLoc_chr = 19
    | Hs_GenLoc_start = 10105023
    | Hs_GenLoc_end = 10166811
    | Hs_Uniprot = P26358
    | Mm_EntrezGene = 13433
    | Mm_Ensembl = ENSMUSG00000004099
    | Mm_RefseqmRNA = NM_010066
    | Mm_RefseqProtein = NP_034196
    | Mm_GenLoc_db = 
    | Mm_GenLoc_chr = 9
    | Mm_GenLoc_start = 20657611
    | Mm_GenLoc_end = 20703267
    | Mm_Uniprot = Q0VDW2
  }}
}}
'''DNA (cytosine-5-)-methyltransferase 1''', also known as '''DNMT1''', is a human [[gene]].


<!-- The PBB_Summary template is automatically maintained by Protein Box Bot. See Template:PBB_Controls to Stop updates. -->
This enzyme is responsible for maintenance DNA methylation which ensures the fidelity of replication of inherited epigenetic patterns. It has a very distinguishable preference of methylating CpGs on hemimethylated DNA.<ref>{{cite journal | vauthors = Hermann A, Goyal R, Jeltsch A | title = The Dnmt1 DNA-(cytosine-C5)-methyltransferase methylates DNA processively with high preference for hemimethylated target sites | journal = The Journal of Biological Chemistry | volume = 279 | issue = 46 | pages = 48350–9 | date = November 2004 | pmid = 15339928 | doi = 10.1074/jbc.M403427200 }}</ref> Aberrant methylation patterns are associated with certain human tumors and developmental abnormalities.<ref name="pmid21532572">{{cite journal | vauthors = 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 | title = Mutations in DNMT1 cause hereditary sensory neuropathy with dementia and hearing loss | journal = Nature Genetics | volume = 43 | issue = 6 | pages = 595–600 | date = June 2011 | pmid = 21532572 | pmc = 3102765 | doi = 10.1038/ng.830 }}</ref><ref>{{cite web | title = Entrez Gene: DNMT1 DNA (cytosine-5-)-methyltransferase 1| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=1786 }}</ref>
{{PBB_Summary
| section_title =  
| summary_text = 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.<ref>{{cite web | title = Entrez Gene: DNMT1 DNA (cytosine-5-)-methyltransferase 1| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=1786| accessdate = }}</ref>
}}


==See also==
== See also ==
* [[DNA methyltransferase]]
* [[DNA methyltransferase]]


==References==
== Interactions ==
{{reflist|2}}
DNMT1 has been shown to [[Protein-protein interaction|interact]] with UHRF1,:
==Further reading==
* [[DMAP1]],<ref name = pmid10888872/>
{{refbegin | 2}}
* [[DNMT3A]]<ref name = pmid12145218>{{cite journal | vauthors = Kim GD, Ni J, Kelesoglu N, Roberts RJ, Pradhan S | title = Co-operation and communication between the human maintenance and de novo DNA (cytosine-5) methyltransferases | journal = The EMBO Journal | volume = 21 | issue = 15 | pages = 4183–95 | date = August 2002 | pmid = 12145218 | pmc = 126147 | doi = 10.1093/emboj/cdf401 }}</ref>
{{PBB_Further_reading
* [[DNMT3B]],<ref name = pmid12145218/><ref name = pmid12867029>{{cite journal | vauthors = Lehnertz B, Ueda Y, Derijck AA, Braunschweig U, Perez-Burgos L, Kubicek S, Chen T, Li E, Jenuwein T, Peters AH | title = Suv39h-mediated histone H3 lysine 9 methylation directs DNA methylation to major satellite repeats at pericentric heterochromatin | journal = Current Biology | volume = 13 | issue = 14 | pages = 1192–200 | date = July 2003 | pmid = 12867029 | doi = 10.1016/s0960-9822(03)00432-9 }}</ref>
| citations =
* [[Histone deacetylase 2|HDAC2]],<ref name = pmid10888872>{{cite journal | vauthors = Rountree MR, Bachman KE, Baylin SB | title = DNMT1 binds HDAC2 and a new co-repressor, DMAP1, to form a complex at replication foci | journal = Nature Genetics | volume = 25 | issue = 3 | pages = 269–77 | date = July 2000 | pmid = 10888872 | doi = 10.1038/77023 }}</ref>
*{{cite journal  | author=Yen RW, Vertino PM, Nelkin BD, ''et al.'' |title=Isolation and characterization of the cDNA encoding human DNA methyltransferase. |journal=Nucleic Acids Res. |volume=20 |issue= 9 |pages= 2287-91 |year= 1992 |pmid= 1594447 |doi= }}
* [[PCNA]],<ref name = pmid10888872/><ref name = pmid12354094>{{cite journal | vauthors = Iida T, Suetake I, Tajima S, Morioka H, Ohta S, Obuse C, Tsurimoto T | title = PCNA clamp facilitates action of DNA cytosine methyltransferase 1 on hemimethylated DNA | journal = Genes to Cells | volume = 7 | issue = 10 | pages = 997–1007 | date = October 2002 | pmid = 12354094 | doi = 10.1046/j.1365-2443.2002.00584.x }}</ref><ref name = pmid9302295>{{cite journal | vauthors = Chuang LS, Ian HI, Koh TW, Ng HH, Xu G, Li BF | title = Human DNA-(cytosine-5) methyltransferase-PCNA complex as a target for p21WAF1 | journal = Science | volume = 277 | issue = 5334 | pages = 1996–2000 | date = September 1997 | pmid = 9302295 | doi = 10.1126/science.277.5334.1996 }}</ref>
*{{cite journal | author=Bestor T, Laudano A, Mattaliano R, Ingram V |title=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=J. Mol. Biol. |volume=203 |issue= 4 |pages= 971-83 |year= 1989 |pmid= 3210246 |doi= }}
* [[Retinoblastoma protein|RB1]].<ref name = pmid10888886>{{cite journal | vauthors = Robertson KD, Ait-Si-Ali S, Yokochi T, Wade PA, Jones PL, Wolffe AP | title = DNMT1 forms a complex with Rb, E2F1 and HDAC1 and represses transcription from E2F-responsive promoters | journal = Nature Genetics | volume = 25 | issue = 3 | pages = 338–42 | date = July 2000 | pmid = 10888886 | doi = 10.1038/77124 }}</ref> and
*{{cite journal | author=Hijmans EM, Voorhoeve PM, Beijersbergen RL, ''et al.'' |title=E2F-5, a new E2F family member that interacts with p130 in vivo. |journal=Mol. Cell. Biol. |volume=15 |issue= 6 |pages= 3082-9 |year= 1995 |pmid= 7760804 |doi= }}
* [[EHMT2|G9A]]<ref name=":0">{{cite journal | vauthors = Estève PO, Chin HG, Smallwood A, Feehery GR, Gangisetty O, Karpf AR, Carey MF, Pradhan S | title = Direct interaction between DNMT1 and G9a coordinates DNA and histone methylation during replication | journal = Genes & Development | volume = 20 | issue = 22 | pages = 3089–103 | date = November 2006 | pmid = 17085482 | pmc = 1635145 | doi = 10.1101/gad.1463706 }}</ref>
*{{cite journal | author=Yoder JA, Yen RW, Vertino PM, ''et al.'' |title=New 5' regions of the murine and human genes for DNA (cytosine-5)-methyltransferase. |journal=J. Biol. Chem. |volume=271 |issue= 49 |pages= 31092-7 |year= 1997 |pmid= 8940105 |doi= }}
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.<ref>{{cite journal | vauthors = Robertson KD, Keyomarsi K, Gonzales FA, Velicescu M, Jones PA | title = Differential mRNA expression of the human DNA methyltransferases (DNMTs) 1, 3a and 3b during the G(0)/G(1) to S phase transition in normal and tumor cells | journal = Nucleic Acids Research | volume = 28 | issue = 10 | pages = 2108–13 | date = May 2000 | pmid = 10773079 | pmc = 105379 | doi=10.1093/nar/28.10.2108}}</ref> Its interaction with PCNA and UHRF1 has been implicated in localizing it to the replication fork.<ref>{{cite journal | vauthors = Jones PA, Liang G | title = Rethinking how DNA methylation patterns are maintained | journal = Nature Reviews. Genetics | volume = 10 | issue = 11 | pages = 805–11 | date = November 2009 | pmid = 19789556 | pmc = 2848124 | doi = 10.1038/nrg2651 }}</ref> The direct co-operation between DNMT1 and G9a coordinates DNA and H3K9 methylation during cell division.<ref name=":0" /> This chromatin methylation is necessary for stable repression of gene expression during mammalian development.
*{{cite journal | author=Chuang LS, Ian HI, Koh TW, ''et al.'' |title=Human DNA-(cytosine-5) methyltransferase-PCNA complex as a target for p21WAF1. |journal=Science |volume=277 |issue= 5334 |pages= 1996-2000 |year= 1997 |pmid= 9302295 |doi= }}
 
*{{cite journal | author=Baylin SB |title=Tying it all together: epigenetics, genetics, cell cycle, and cancer. |journal=Science |volume=277 |issue= 5334 |pages= 1948-9 |year= 1997 |pmid= 9333948 |doi= }}
== Model organisms ==
*{{cite journal | author=Robertson KD, Uzvolgyi E, Liang G, ''et al.'' |title=The human DNA methyltransferases (DNMTs) 1, 3a and 3b: coordinate mRNA expression in normal tissues and overexpression in tumors. |journal=Nucleic Acids Res. |volume=27 |issue= 11 |pages= 2291-8 |year= 1999 |pmid= 10325416 |doi= }}
Knockout experiments have shown that this enzyme is responsible for the bulk of methylation in mouse cells, and it is essential for embryonic development.<ref>{{cite journal | vauthors = Li E, Bestor TH, Jaenisch R | title = Targeted mutation of the DNA methyltransferase gene results in embryonic lethality | journal = Cell | volume = 69 | issue = 6 | pages = 915–26 | date = June 1992 | pmid = 1606615 | doi = 10.1016/0092-8674(92)90611-F }}</ref> It has also been shown that a lack of both maternal and zygotic ''Dnmt1'' results in complete demethylation of imprinted genes in blastocysts.<ref>{{cite journal | vauthors = Hirasawa R, Chiba H, Kaneda M, Tajima S, Li E, Jaenisch R, Sasaki H | title = Maternal and zygotic Dnmt1 are necessary and sufficient for the maintenance of DNA methylation imprints during preimplantation development | journal = Genes & Development | volume = 22 | issue = 12 | pages = 1607–16 | date = June 2008 | pmid = 18559477 | pmc = 2428059 | doi = 10.1101/gad.1667008 }}</ref>
*{{cite journal | author=Michaelson JS, Bader D, Kuo F, ''et al.'' |title=Loss of Daxx, a promiscuously interacting protein, results in extensive apoptosis in early mouse development. |journal=Genes Dev. |volume=13 |issue= 15 |pages= 1918-23 |year= 1999 |pmid= 10444590 |doi= }}
 
*{{cite journal | author=Hsu DW, Lin MJ, Lee TL, ''et al.'' |title=Two major forms of DNA (cytosine-5) methyltransferase in human somatic tissues. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=96 |issue= 17 |pages= 9751-6 |year= 1999 |pmid= 10449766 |doi= }}
== Clinical significance ==
*{{cite journal  | author=Fuks F, Burgers WA, Brehm A, ''et al.'' |title=DNA methyltransferase Dnmt1 associates with histone deacetylase activity. |journal=Nat. Genet. |volume=24 |issue= 1 |pages= 88-91 |year= 2000 |pmid= 10615135 |doi= 10.1038/71750 }}
DNMT1 plays a critical role in Hematopoietic stem cell (HSC) maintenance. HSCs with reduced DNMT1 fail to self-renew efficiently post-transplantation.<ref>{{cite journal | vauthors = Trowbridge JJ, Snow JW, Kim J, Orkin SH | title = DNA methyltransferase 1 is essential for and uniquely regulates hematopoietic stem and progenitor cells | journal = Cell Stem Cell | volume = 5 | issue = 4 | pages = 442–9 | date = October 2009 | pmid = 19796624 | pmc = 2767228 | doi = 10.1016/j.stem.2009.08.016 }}</ref> 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.<ref>{{cite journal | vauthors = Avgustinova A, Benitah SA | title = Epigenetic control of adult stem cell function | journal = Nature Reviews. Molecular Cell Biology | volume = 17 | issue = 10 | pages = 643–58 | date = October 2016 | pmid = 27405257 | doi = 10.1038/nrm.2016.76 }}</ref>
*{{cite journal | author=Bonfils C, Beaulieu N, Chan E, ''et al.'' |title=Characterization of the human DNA methyltransferase splice variant Dnmt1b. |journal=J. Biol. Chem. |volume=275 |issue= 15 |pages= 10754-60 |year= 2000 |pmid= 10753866 |doi= }}
 
*{{cite journal | author=Rountree MR, Bachman KE, Baylin SB |title=DNMT1 binds HDAC2 and a new co-repressor, DMAP1, to form a complex at replication foci. |journal=Nat. Genet. |volume=25 |issue= 3 |pages= 269-77 |year= 2000 |pmid= 10888872 |doi= 10.1038/77023 }}
== References ==
*{{cite journal  | author=Robertson KD, Ait-Si-Ali S, Yokochi T, ''et al.'' |title=DNMT1 forms a complex with Rb, E2F1 and HDAC1 and represses transcription from E2F-responsive promoters. |journal=Nat. Genet. |volume=25 |issue= 3 |pages= 338-42 |year= 2000 |pmid= 10888886 |doi= 10.1038/77124 }}
{{reflist|33em}}
*{{cite journal  | author=Tatematsu KI, Yamazaki T, Ishikawa F |title=MBD2-MBD3 complex binds to hemi-methylated DNA and forms a complex containing DNMT1 at the replication foci in late S phase. |journal=Genes Cells |volume=5 |issue= 8 |pages= 677-88 |year= 2000 |pmid= 10947852 |doi= }}
 
*{{cite journal | author=Mizuno  S, Chijiwa T, Okamura T, ''et al.'' |title=Expression of DNA methyltransferases DNMT1, 3A, and 3B in normal hematopoiesis and in acute and chronic myelogenous leukemia. |journal=Blood |volume=97 |issue= 5 |pages= 1172-9 |year= 2001 |pmid= 11222358 |doi= }}
== Further reading ==
*{{cite journal | author=Fatemi M, Hermann A, Pradhan S, Jeltsch A |title=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. |journal=J. Mol. Biol. |volume=309 |issue= 5 |pages= 1189-99 |year= 2001 |pmid= 11399088 |doi= 10.1006/jmbi.2001.4709 }}
{{refbegin|33em}}
*{{cite journal | author=Dintilhac A, Bernués J |title=HMGB1 interacts with many apparently unrelated proteins by recognizing short amino acid sequences. |journal=J. Biol. Chem. |volume=277 |issue= 9 |pages= 7021-8 |year= 2002 |pmid= 11748221 |doi= 10.1074/jbc.M108417200 }}
* {{cite journal | vauthors = Smith SS, Kaplan BE, Sowers LC, Newman EM | title = Mechanism of human methyl-directed DNA methyltransferase and the fidelity of cytosine methylation | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 89 | issue = 10 | pages = 4744–8 | date = May 1992 | pmid = 1584813 | pmc = 49160 | doi = 10.1073/pnas.89.10.4744 }}
*{{cite journal | author=Di Croce L, Raker VA, Corsaro M, ''et al.'' |title=Methyltransferase recruitment and DNA hypermethylation of target promoters by an oncogenic transcription factor. |journal=Science |volume=295 |issue= 5557 |pages= 1079-82 |year= 2002 |pmid= 11834837 |doi= 10.1126/science.1065173 }}
* {{cite journal | vauthors = Bestor T, Laudano A, Mattaliano R, Ingram V | title = 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 = Journal of Molecular Biology | volume = 203 | issue = 4 | pages = 971–83 | date = October 1988 | pmid = 3210246 | doi = 10.1016/0022-2836(88)90122-2 }}
*{{cite journal | author=Pradhan S, Kim GD |title=The retinoblastoma gene product interacts with maintenance human DNA (cytosine-5) methyltransferase and modulates its activity. |journal=EMBO J. |volume=21 |issue= 4 |pages= 779-88 |year= 2002 |pmid= 11847125 |doi= 10.1093/emboj/21.4.779 }}
* {{cite journal | vauthors = Smith SS | title = Biological implications of the mechanism of action of human DNA (cytosine-5)methyltransferase | journal = Progress in Nucleic Acid Research and Molecular Biology | volume = 49 | pages = 65–111 | year = 1994 | pmid = 7863011 }}
*{{cite journal | author=Rhee I, Bachman KE, Park BH, ''et al.'' |title=DNMT1 and DNMT3b cooperate to silence genes in human cancer cells. |journal=Nature |volume=416 |issue= 6880 |pages= 552-6 |year= 2002 |pmid= 11932749 |doi= 10.1038/416552a }}
* {{cite journal | vauthors = Hijmans EM, Voorhoeve PM, Beijersbergen RL, van 't Veer LJ, Bernards R | title = E2F-5, a new E2F family member that interacts with p130 in vivo | journal = Molecular and Cellular Biology | volume = 15 | issue = 6 | pages = 3082–9 | date = June 1995 | pmid = 7760804 | pmc = 230539 | doi = 10.1128/mcb.15.6.3082 }}
}}
* {{cite journal | vauthors = Yoder JA, Yen RW, Vertino PM, Bestor TH, Baylin SB | title = New 5' regions of the murine and human genes for DNA (cytosine-5)-methyltransferase | journal = The Journal of Biological Chemistry | volume = 271 | issue = 49 | pages = 31092–7 | date = December 1996 | pmid = 8940105 | doi = 10.1074/jbc.271.49.31092 }}
* {{cite journal | vauthors = Chuang LS, Ian HI, Koh TW, Ng HH, Xu G, Li BF | title = Human DNA-(cytosine-5) methyltransferase-PCNA complex as a target for p21WAF1 | journal = Science | volume = 277 | issue = 5334 | pages = 1996–2000 | date = September 1997 | pmid = 9302295 | doi = 10.1126/science.277.5334.1996 }}
* {{cite journal | vauthors = Kho MR, Baker DJ, Laayoun A, Smith SS | title = Stalling of human DNA (cytosine-5) methyltransferase at single-strand conformers from a site of dynamic mutation | journal = Journal of Molecular Biology | volume = 275 | issue = 1 | pages = 67–79 | date = January 1998 | pmid = 9451440 | doi = 10.1006/jmbi.1997.1430 }}
* {{cite journal | vauthors = Baylin SB | title = Tying it all together: epigenetics, genetics, cell cycle, and cancer | journal = Science | volume = 277 | issue = 5334 | pages = 1948–9 | date = September 1997 | pmid = 9333948 | doi = 10.1126/science.277.5334.1948 }}
* {{cite journal | vauthors = Robertson KD, Uzvolgyi E, Liang G, Talmadge C, Sumegi J, Gonzales FA, Jones PA | title = The human DNA methyltransferases (DNMTs) 1, 3a and 3b: coordinate mRNA expression in normal tissues and overexpression in tumors | journal = Nucleic Acids Research | volume = 27 | issue = 11 | pages = 2291–8 | date = June 1999 | pmid = 10325416 | pmc = 148793 | doi = 10.1093/nar/27.11.2291 }}
* {{cite journal | vauthors = Michaelson JS, Bader D, Kuo F, Kozak C, Leder P | title = Loss of Daxx, a promiscuously interacting protein, results in extensive apoptosis in early mouse development | journal = Genes & Development | volume = 13 | issue = 15 | pages = 1918–23 | date = August 1999 | pmid = 10444590 | pmc = 316925 | doi = 10.1101/gad.13.15.1918 }}
* {{cite journal | vauthors = Hsu DW, Lin MJ, Lee TL, Wen SC, Chen X, Shen CK | title = Two major forms of DNA (cytosine-5) methyltransferase in human somatic tissues | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 96 | issue = 17 | pages = 9751–6 | date = August 1999 | pmid = 10449766 | pmc = 22282 | doi = 10.1073/pnas.96.17.9751 }}
* {{cite journal | vauthors = Fuks F, Burgers WA, Brehm A, Hughes-Davies L, Kouzarides T | title = DNA methyltransferase Dnmt1 associates with histone deacetylase activity | journal = Nature Genetics | volume = 24 | issue = 1 | pages = 88–91 | date = January 2000 | pmid = 10615135 | doi = 10.1038/71750 }}
* {{cite journal | vauthors = Bonfils C, Beaulieu N, Chan E, Cotton-Montpetit J, MacLeod AR | title = Characterization of the human DNA methyltransferase splice variant Dnmt1b | journal = The Journal of Biological Chemistry | volume = 275 | issue = 15 | pages = 10754–60 | date = April 2000 | pmid = 10753866 | doi = 10.1074/jbc.275.15.10754 }}
* {{cite journal | vauthors = Rountree MR, Bachman KE, Baylin SB | title = DNMT1 binds HDAC2 and a new co-repressor, DMAP1, to form a complex at replication foci | journal = Nature Genetics | volume = 25 | issue = 3 | pages = 269–77 | date = July 2000 | pmid = 10888872 | doi = 10.1038/77023 }}
* {{cite journal | vauthors = Robertson KD, Ait-Si-Ali S, Yokochi T, Wade PA, Jones PL, Wolffe AP | title = DNMT1 forms a complex with Rb, E2F1 and HDAC1 and represses transcription from E2F-responsive promoters | journal = Nature Genetics | volume = 25 | issue = 3 | pages = 338–42 | date = July 2000 | pmid = 10888886 | doi = 10.1038/77124 }}
* {{cite journal | vauthors = Tatematsu KI, Yamazaki T, Ishikawa F | title = MBD2-MBD3 complex binds to hemi-methylated DNA and forms a complex containing DNMT1 at the replication foci in late S phase | journal = Genes to Cells | volume = 5 | issue = 8 | pages = 677–88 | date = August 2000 | pmid = 10947852 | doi = 10.1046/j.1365-2443.2000.00359.x }}
* {{cite journal | vauthors = Mizuno S, Chijiwa T, Okamura T, Akashi K, Fukumaki Y, Niho Y, Sasaki H | title = Expression of DNA methyltransferases DNMT1, 3A, and 3B in normal hematopoiesis and in acute and chronic myelogenous leukemia | journal = Blood | volume = 97 | issue = 5 | pages = 1172–9 | date = March 2001 | pmid = 11222358 | doi = 10.1182/blood.V97.5.1172 }}
* {{cite journal | vauthors = Fatemi M, Hermann A, Pradhan S, Jeltsch A | title = 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 | journal = Journal of Molecular Biology | volume = 309 | issue = 5 | pages = 1189–99 | date = June 2001 | pmid = 11399088 | doi = 10.1006/jmbi.2001.4709 }}
* {{cite journal | vauthors = Dintilhac A, Bernués J | title = HMGB1 interacts with many apparently unrelated proteins by recognizing short amino acid sequences | journal = The Journal of Biological Chemistry | volume = 277 | issue = 9 | pages = 7021–8 | date = March 2002 | pmid = 11748221 | doi = 10.1074/jbc.M108417200 }}
* {{cite journal | vauthors = 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 | title = Methyltransferase recruitment and DNA hypermethylation of target promoters by an oncogenic transcription factor | journal = Science | volume = 295 | issue = 5557 | pages = 1079–82 | date = February 2002 | pmid = 11834837 | doi = 10.1126/science.1065173 }}
* {{cite journal | vauthors = Pradhan S, Kim GD | title = The retinoblastoma gene product interacts with maintenance human DNA (cytosine-5) methyltransferase and modulates its activity | journal = The EMBO Journal | volume = 21 | issue = 4 | pages = 779–88 | date = February 2002 | pmid = 11847125 | pmc = 125847 | doi = 10.1093/emboj/21.4.779 }}
* {{cite journal | vauthors = Rhee I, Bachman KE, Park BH, Jair KW, Yen RW, Schuebel KE, Cui H, Feinberg AP, Lengauer C, Kinzler KW, Baylin SB, Vogelstein B | title = DNMT1 and DNMT3b cooperate to silence genes in human cancer cells | journal = Nature | volume = 416 | issue = 6880 | pages = 552–6 | date = April 2002 | pmid = 11932749 | doi = 10.1038/416552a }}
* {{cite journal | vauthors = Jair KW, Bachman KE, Suzuki H, Ting AH, Rhee I, Yen RW, Baylin SB, Schuebel KE | title = De novo CpG island methylation in human cancer cells | journal = Cancer Research | volume = 66 | issue = 2 | pages = 682–92 | date = January 2006 | pmid = 16423997 | doi = 10.1158/0008-5472.CAN-05-1980 }}
* {{cite journal | vauthors = Ting AH, Jair KW, Schuebel KE, Baylin SB | title = Differential requirement for DNA methyltransferase 1 in maintaining human cancer cell gene promoter hypermethylation | journal = Cancer Research | volume = 66 | issue = 2 | pages = 729–35 | date = January 2006 | pmid = 16424002 | doi = 10.1158/0008-5472.CAN-05-1537 }}
* {{cite journal | vauthors = Svedruzić ZM | title = Mammalian cytosine DNA methyltransferase Dnmt1: enzymatic mechanism, novel mechanism-based inhibitors, and RNA-directed DNA methylation | journal = Current Medicinal Chemistry | volume = 15 | issue = 1 | pages = 92–106 | year = 2008 | pmid = 18220765 | doi = 10.2174/092986708783330700 | url = http://www.bolnicarab.hr/upload/Svedruzic/referenca%204.pdf }}
* {{cite journal | vauthors = Bestor T, Laudano A, Mattaliano R, Ingram V | title = 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 = Journal of Molecular Biology | volume = 203 | issue = 4 | pages = 971–83 | date = October 1988 | pmid = 3210246 | doi = 10.1016/0022-2836(88)90122-2 }}
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== External links ==
{{WikiDoc Sources}}
* [https://www.ncbi.nlm.nih.gov/books/NBK84112/  GeneReviews/NCBI/NIH/UW entry on DNMT1-Related Dementia, Deafness, and Sensory Neuropathy]

Latest revision as of 18:39, 30 August 2017

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DNA (cytosine-5)-methyltransferase 1 is an enzyme that catalyzes the transfer of methyl groups to specific CpG structures in DNA, a process called DNA methylation. In humans, it is encoded by the DNMT1 gene.[1] DNMT1 forms part of the family of DNA methyltransferase enzymes, which consists primarily of DNMT1, DNMT3A, and DNMT3B.

Function

This enzyme is responsible for maintenance DNA methylation which ensures the fidelity of replication of inherited epigenetic patterns. It has a very distinguishable preference of methylating CpGs on hemimethylated DNA.[2] Aberrant methylation patterns are associated with certain human tumors and developmental abnormalities.[3][4]

See also

Interactions

DNMT1 has been shown to interact with UHRF1,:

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.[12] Its interaction with PCNA and UHRF1 has been implicated in localizing it to the replication fork.[13] The direct co-operation between DNMT1 and G9a coordinates DNA and H3K9 methylation during cell division.[11] This chromatin methylation is necessary for stable repression of gene expression during mammalian development.

Model organisms

Knockout experiments have shown that this enzyme is responsible for the bulk of methylation in mouse cells, and it is essential for embryonic development.[14] It has also been shown that a lack of both maternal and zygotic Dnmt1 results in complete demethylation of imprinted genes in blastocysts.[15]

Clinical significance

DNMT1 plays a critical role in Hematopoietic stem cell (HSC) maintenance. HSCs with reduced DNMT1 fail to self-renew efficiently post-transplantation.[16] 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.[17]

References

  1. ↑ Yen RW, Vertino PM, Nelkin BD, Yu JJ, el-Deiry W, Cumaraswamy A, Lennon GG, Trask BJ, Celano P, Baylin SB (May 1992). "Isolation and characterization of the cDNA encoding human DNA methyltransferase". Nucleic Acids Research. 20 (9): 2287–91. doi:10.1093/nar/20.9.2287. PMC 312343. PMID 1594447.
  2. ↑ Hermann A, Goyal R, Jeltsch A (November 2004). "The Dnmt1 DNA-(cytosine-C5)-methyltransferase methylates DNA processively with high preference for hemimethylated target sites". The Journal of Biological Chemistry. 279 (46): 48350–9. doi:10.1074/jbc.M403427200. PMID 15339928.
  3. ↑ 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 (June 2011). "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.
  4. ↑ "Entrez Gene: DNMT1 DNA (cytosine-5-)-methyltransferase 1".
  5. ↑ 5.0 5.1 5.2 Rountree MR, Bachman KE, Baylin SB (July 2000). "DNMT1 binds HDAC2 and a new co-repressor, DMAP1, to form a complex at replication foci". Nature Genetics. 25 (3): 269–77. doi:10.1038/77023. PMID 10888872.
  6. ↑ 6.0 6.1 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". The EMBO Journal. 21 (15): 4183–95. doi:10.1093/emboj/cdf401. PMC 126147. PMID 12145218.
  7. ↑ 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". Current Biology. 13 (14): 1192–200. doi:10.1016/s0960-9822(03)00432-9. PMID 12867029.
  8. ↑ 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 to Cells. 7 (10): 997–1007. doi:10.1046/j.1365-2443.2002.00584.x. PMID 12354094.
  9. ↑ 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.
  10. ↑ 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". Nature Genetics. 25 (3): 338–42. doi:10.1038/77124. PMID 10888886.
  11. ↑ 11.0 11.1 Estève PO, Chin HG, Smallwood A, Feehery GR, Gangisetty O, Karpf AR, Carey MF, Pradhan S (November 2006). "Direct interaction between DNMT1 and G9a coordinates DNA and histone methylation during replication". Genes & Development. 20 (22): 3089–103. doi:10.1101/gad.1463706. PMC 1635145. PMID 17085482.
  12. ↑ Robertson KD, Keyomarsi K, Gonzales FA, Velicescu M, Jones PA (May 2000). "Differential mRNA expression of the human DNA methyltransferases (DNMTs) 1, 3a and 3b during the G(0)/G(1) to S phase transition in normal and tumor cells". Nucleic Acids Research. 28 (10): 2108–13. doi:10.1093/nar/28.10.2108. PMC 105379. PMID 10773079.
  13. ↑ Jones PA, Liang G (November 2009). "Rethinking how DNA methylation patterns are maintained". Nature Reviews. Genetics. 10 (11): 805–11. doi:10.1038/nrg2651. PMC 2848124. PMID 19789556.
  14. ↑ Li E, Bestor TH, Jaenisch R (June 1992). "Targeted mutation of the DNA methyltransferase gene results in embryonic lethality". Cell. 69 (6): 915–26. doi:10.1016/0092-8674(92)90611-F. PMID 1606615.
  15. ↑ Hirasawa R, Chiba H, Kaneda M, Tajima S, Li E, Jaenisch R, Sasaki H (June 2008). "Maternal and zygotic Dnmt1 are necessary and sufficient for the maintenance of DNA methylation imprints during preimplantation development". Genes & Development. 22 (12): 1607–16. doi:10.1101/gad.1667008. PMC 2428059. PMID 18559477.
  16. ↑ Trowbridge JJ, Snow JW, Kim J, Orkin SH (October 2009). "DNA methyltransferase 1 is essential for and uniquely regulates hematopoietic stem and progenitor cells". Cell Stem Cell. 5 (4): 442–9. doi:10.1016/j.stem.2009.08.016. PMC 2767228. PMID 19796624.
  17. ↑ Avgustinova A, Benitah SA (October 2016). "Epigenetic control of adult stem cell function". Nature Reviews. Molecular Cell Biology. 17 (10): 643–58. doi:10.1038/nrm.2016.76. PMID 27405257.

Further reading

External links

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