User:Xiang Chen/Sandbox 10
From Proteopedia
< User:Xiang Chen(Difference between revisions)
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== Function == | == Function == | ||
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All three TET enzymes and their isoforms are involved in the biochemical pathway that converts 5-methylcytosine (5mC) into 5-hydroxymethylcytosine (5hmC). They also regulate the further conversions of 5hmC to 5-formylcytosine (5fC) and then 5fC to 5-carboxylcytosine (5caC).<ref name='He et al.'>DOI: 10.1126/science.1210944</ref> Although experimental data shows that TET3 does so to a lesser extent than TET1 and TET2.<ref name='He et al.' /> | All three TET enzymes and their isoforms are involved in the biochemical pathway that converts 5-methylcytosine (5mC) into 5-hydroxymethylcytosine (5hmC). They also regulate the further conversions of 5hmC to 5-formylcytosine (5fC) and then 5fC to 5-carboxylcytosine (5caC).<ref name='He et al.'>DOI: 10.1126/science.1210944</ref> Although experimental data shows that TET3 does so to a lesser extent than TET1 and TET2.<ref name='He et al.' /> | ||
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While the oxidation performed by TET enzymes was originally thought to be a source of DNA damage, new research has implied that this catalytic activity may actually be the initial steps of a process of DNA demethylation. This hypothesized DNA demethylation pathway starts with the conversion of 5mC to 5caC after several rounds of oxidation by TET enzymes. The next step is the removal of the modified cytosine base by thymine DNA glycosylase (TDG) which leaves an abasic site on the DNA. The last step is then the process of base excision repair in which a new unmodified cytosine is regenerated at the site, thus completing the process of DNA demethylation.<ref name='He et al.' /><ref name='Rahul M. Kohli & Yi Zhang'>DOI 10.1038/nature12750</ref> | While the oxidation performed by TET enzymes was originally thought to be a source of DNA damage, new research has implied that this catalytic activity may actually be the initial steps of a process of DNA demethylation. This hypothesized DNA demethylation pathway starts with the conversion of 5mC to 5caC after several rounds of oxidation by TET enzymes. The next step is the removal of the modified cytosine base by thymine DNA glycosylase (TDG) which leaves an abasic site on the DNA. The last step is then the process of base excision repair in which a new unmodified cytosine is regenerated at the site, thus completing the process of DNA demethylation.<ref name='He et al.' /><ref name='Rahul M. Kohli & Yi Zhang'>DOI 10.1038/nature12750</ref> | ||
| - | ===Specific Functions=== | ||
Experimental data shows that the TET genes have different expression patterns and at different levels, which indicates that each of the TET enzymes do not fully overlap in their functionality. | Experimental data shows that the TET genes have different expression patterns and at different levels, which indicates that each of the TET enzymes do not fully overlap in their functionality. | ||
Current revision
TET Enzymes
TET enzymes are a family of dioxygenases that are involved in the process of oxidizing methylated cytosine. Members of this family include ten-eleven translocation methylcytosine dioxygenase 1 (TET1), methylcytosine dioxygenase TET2, and methylcytosine dioxygenase TET3. The gene for the first of these proteins, TET1, was identified when it was determined to be fused to the Mixed Lineage Leukemia (MLL) gene as a result of a translocation event that occurred between chromosomes ten and eleven (hence the name). [1]
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References
- ↑ Lorsbach RB, Moore J, Mathew S, Raimondi SC, Mukatira ST, Downing JR. TET1, a member of a novel protein family, is fused to MLL in acute myeloid leukemia containing the t(10;11)(q22;q23). Leukemia. 2003 Mar;17(3):637-41. PMID:12646957 doi:http://dx.doi.org/10.1038/sj.leu.2402834
- ↑ 2.0 2.1 Kinney SR, Pradhan S. Ten eleven translocation enzymes and 5-hydroxymethylation in mammalian development and cancer. Adv Exp Med Biol. 2013;754:57-79. doi: 10.1007/978-1-4419-9967-2_3. PMID:22956496 doi:http://dx.doi.org/10.1007/978-1-4419-9967-2_3
- ↑ 3.0 3.1 Frauer C, Rottach A, Meilinger D, Bultmann S, Fellinger K, Hasenoder S, Wang M, Qin W, Soding J, Spada F, Leonhardt H. Different binding properties and function of CXXC zinc finger domains in Dnmt1 and Tet1. PLoS One. 2011 Feb 2;6(2):e16627. doi: 10.1371/journal.pone.0016627. PMID:21311766 doi:http://dx.doi.org/10.1371/journal.pone.0016627
- ↑ 4.0 4.1 4.2 He YF, Li BZ, Li Z, Liu P, Wang Y, Tang Q, Ding J, Jia Y, Chen Z, Li L, Sun Y, Li X, Dai Q, Song CX, Zhang K, He C, Xu GL. Tet-mediated formation of 5-carboxylcytosine and its excision by TDG in mammalian DNA. Science. 2011 Sep 2;333(6047):1303-7. doi: 10.1126/science.1210944. Epub 2011 Aug, 4. PMID:21817016 doi:http://dx.doi.org/10.1126/science.1210944
- ↑ 5.0 5.1 Kohli RM, Zhang Y. TET enzymes, TDG and the dynamics of DNA demethylation. Nature. 2013 Oct 24;502(7472):472-9. doi: 10.1038/nature12750. PMID:24153300 doi:http://dx.doi.org/10.1038/nature12750
- ↑ Takai H, Masuda K, Sato T, Sakaguchi Y, Suzuki T, Suzuki T, Koyama-Nasu R, Nasu-Nishimura Y, Katou Y, Ogawa H, Morishita Y, Kozuka-Hata H, Oyama M, Todo T, Ino Y, Mukasa A, Saito N, Toyoshima C, Shirahige K, Akiyama T. 5-Hydroxymethylcytosine plays a critical role in glioblastomagenesis by recruiting the CHTOP-methylosome complex. Cell Rep. 2014 Oct 9;9(1):48-60. doi: 10.1016/j.celrep.2014.08.071. Epub 2014 Oct, 2. PMID:25284789 doi:http://dx.doi.org/10.1016/j.celrep.2014.08.071
- ↑ doi: https://dx.doi.org/10.1182/blood-2009-03-210039
- ↑ Delhommeau F, Dupont S, Della Valle V, James C, Trannoy S, Masse A, Kosmider O, Le Couedic JP, Robert F, Alberdi A, Lecluse Y, Plo I, Dreyfus FJ, Marzac C, Casadevall N, Lacombe C, Romana SP, Dessen P, Soulier J, Viguie F, Fontenay M, Vainchenker W, Bernard OA. Mutation in TET2 in myeloid cancers. N Engl J Med. 2009 May 28;360(22):2289-301. doi: 10.1056/NEJMoa0810069. PMID:19474426 doi:http://dx.doi.org/10.1056/NEJMoa0810069
- ↑ Langemeijer SM, Kuiper RP, Berends M, Knops R, Aslanyan MG, Massop M, Stevens-Linders E, van Hoogen P, van Kessel AG, Raymakers RA, Kamping EJ, Verhoef GE, Verburgh E, Hagemeijer A, Vandenberghe P, de Witte T, van der Reijden BA, Jansen JH. Acquired mutations in TET2 are common in myelodysplastic syndromes. Nat Genet. 2009 Jul;41(7):838-42. doi: 10.1038/ng.391. Epub 2009 May 31. PMID:19483684 doi:http://dx.doi.org/10.1038/ng.391
