DNMT3A
From Wikipedia, the free encyclopedia
DNA (cytosine-5)-methyltransferase 3A is an enzyme that catalyzes the transfer of methyl groups to specific CpG structures in DNA, a process called DNA methylation. The enzyme is encoded in humans by the DNMT3A gene.[1][2]
CpG methylation is an epigenetic modification that is important for embryonic development, imprinting, and X-chromosome inactivation. Studies in mice have demonstrated that DNA methylation is required for mammalian development. This gene encodes a DNA methyltransferase that is thought to function in de novo methylation, rather than the maintenance of existing methylated sites. The protein localizes to the cytoplasm and nucleus and its expression is developmentally regulated. Alternative splicing results in multiple transcript variants encoding different isoforms.[3]
Clinical relevance
The study of this gene in mice has shown its reduced expression in ageing animals causes cognitive long-term memory decline.[4]
Interactions
DNMT3A has been shown to interact with ZNF238,[5] HDAC1,[5] Myc,[6] Protein inhibitor of activated STAT2,[7] DNMT1,[8] DNMT3B,[7][8][9] PIAS1,[7] UBE2I[7] and SUV39H1.[10]
References
- ↑ Okano M, Xie S, Li E (July 1998). "Cloning and characterization of a family of novel mammalian DNA (cytosine-5) methyltransferases". Nat Genet 19 (3): 219–20. doi:10.1038/890. PMID 9662389.
- ↑ Xie S, Wang Z, Okano M, Nogami M, Li Y, He WW, Okumura K, Li E (September 1999). "Cloning, expression and chromosome locations of the human DNMT3 gene family". Gene 236 (1): 87–95. doi:10.1016/S0378-1119(99)00252-8. PMID 10433969.
- ↑ "Entrez Gene: DNMT3A DNA (cytosine-5-)-methyltransferase 3 alpha".
- ↑ Oliveira, Ana M M; Hemstedt, Thekla J; Bading, Hilmar. "Rescue of aging-associated decline in Dnmt3a2 expression restores cognitive abilities". Nature Neuroscience. doi:10.1038/nn.3151.
- ↑ 5.0 5.1 Fuks, F; Burgers W A, Godin N, Kasai M, Kouzarides T (May 2001). "Dnmt3a binds deacetylases and is recruited by a sequence-specific repressor to silence transcription". EMBO J. (England) 20 (10): 2536–44. doi:10.1093/emboj/20.10.2536. ISSN 0261-4189. PMC 125250. PMID 11350943.
- ↑ Brenner, Carmen; Deplus Rachel, Didelot Céline, Loriot Axelle, Viré Emmanuelle, De Smet Charles, Gutierrez Arantxa, Danovi Davide, Bernard David, Boon Thierry, Pelicci Pier Giuseppe, Amati Bruno, Kouzarides Tony, de Launoit Yvan, Di Croce Luciano, Fuks François (January 2005). "Myc represses transcription through recruitment of DNA methyltransferase corepressor". EMBO J. (England) 24 (2): 336–46. doi:10.1038/sj.emboj.7600509. ISSN 0261-4189. PMC 545804. PMID 15616584.
- ↑ 7.0 7.1 7.2 7.3 Ling, Yan; Sankpal Umesh T, Robertson Andrea K, McNally James G, Karpova Tatiana, Robertson Keith D (2004). "Modification of de novo DNA methyltransferase 3a (Dnmt3a) by SUMO-1 modulates its interaction with histone deacetylases (HDACs) and its capacity to repress transcription". Nucleic Acids Res. (England) 32 (2): 598–610. doi:10.1093/nar/gkh195. PMC 373322. PMID 14752048.
- ↑ 8.0 8.1 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.
- ↑ 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.
- ↑ Fuks, François; Hurd Paul J, Deplus Rachel, Kouzarides Tony (May 2003). "The DNA methyltransferases associate with HP1 and the SUV39H1 histone methyltransferase". Nucleic Acids Res. (England) 31 (9): 2305–12. doi:10.1093/nar/gkg332. PMC 154218. PMID 12711675.
Further reading
- Adams MD, Kerlavage AR, Fleischmann RD, et al. (1995). "Initial assessment of human gene diversity and expression patterns based upon 83 million nucleotides of cDNA sequence." (PDF). Nature 377 (6547 Suppl): 3–174. PMID 7566098.
- Bonaldo MF, Lennon G, Soares MB (1997). "Normalization and subtraction: two approaches to facilitate gene discovery.". Genome Res. 6 (9): 791–806. doi:10.1101/gr.6.9.791. PMID 8889548.
- 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.
- Fuks F, Burgers WA, Godin N, et al. (2001). "Dnmt3a binds deacetylases and is recruited by a sequence-specific repressor to silence transcription.". EMBO J. 20 (10): 2536–44. doi:10.1093/emboj/20.10.2536. PMC 125250. PMID 11350943.
- Vaute O, Nicolas E, Vandel L, Trouche D (2002). "Functional and physical interaction between the histone methyl transferase Suv39H1 and histone deacetylases.". Nucleic Acids Res. 30 (2): 475–81. doi:10.1093/nar/30.2.475. PMC 99834. PMID 11788710.
- 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.
- Hata K, Okano M, Lei H, Li E (2002). "Dnmt3L cooperates with the Dnmt3 family of de novo DNA methyltransferases to establish maternal imprints in mice.". Development 129 (8): 1983–93. PMID 11934864.
- Chen T, Ueda Y, Xie S, Li E (2002). "A novel Dnmt3a isoform produced from an alternative promoter localizes to euchromatin and its expression correlates with active de novo methylation.". J. Biol. Chem. 277 (41): 38746–54. doi:10.1074/jbc.M205312200. PMID 12138111.
- Kim GD, Ni J, Kelesoglu N, et al. (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.
- Yanagisawa Y, Ito E, Yuasa Y, Maruyama K (2002). "The human DNA methyltransferases DNMT3A and DNMT3B have two types of promoters with different CpG contents.". Biochim. Biophys. Acta 1577 (3): 457–65. doi:10.1016/S0167-4781(02)00482-7. PMID 12359337.
- Fatemi M, Hermann A, Gowher H, Jeltsch A (2002). "Dnmt3a and Dnmt1 functionally cooperate during de novo methylation of DNA.". Eur. J. Biochem. 269 (20): 4981–4. doi:10.1046/j.1432-1033.2002.03198.x. PMID 12383256.
- Weisenberger DJ, Velicescu M, Preciado-Lopez MA, et al. (2003). "Identification and characterization of alternatively spliced variants of DNA methyltransferase 3a in mammalian cells.". Gene 298 (1): 91–9. doi:10.1016/S0378-1119(02)00976-9. PMID 12406579.
- Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences.". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932.
- Chedin F, Lieber MR, Hsieh CL (2003). "The DNA methyltransferase-like protein DNMT3L stimulates de novo methylation by Dnmt3a.". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16916–21. doi:10.1073/pnas.262443999. PMC 139244. PMID 12481029.
- Robert MF, Morin S, Beaulieu N, et al. (2003). "DNMT1 is required to maintain CpG methylation and aberrant gene silencing in human cancer cells.". Nat. Genet. 33 (1): 61–5. doi:10.1038/ng1068. PMID 12496760.
- Fuks F, Hurd PJ, Deplus R, Kouzarides T (2003). "The DNA methyltransferases associate with HP1 and the SUV39H1 histone methyltransferase.". Nucleic Acids Res. 31 (9): 2305–12. doi:10.1093/nar/gkg332. PMC 154218. PMID 12711675.
- Yakushiji T, Uzawa K, Shibahara T, et al. (2003). "Over-expression of DNA methyltransferases and CDKN2A gene methylation status in squamous cell carcinoma of the oral cavity.". Int. J. Oncol. 22 (6): 1201–7. PMID 12738984.
- Ling Y, Sankpal UT, Robertson AK, et al. (2004). "Modification of de novo DNA methyltransferase 3a (Dnmt3a) by SUMO-1 modulates its interaction with histone deacetylases (HDACs) and its capacity to repress transcription.". Nucleic Acids Res. 32 (2): 598–610. doi:10.1093/nar/gkh195. PMC 373322. PMID 14752048.
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