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Gene Review

DNMT3A  -  DNA (cytosine-5-)-methyltransferase 3 alpha

Homo sapiens

Synonyms: DNA (cytosine-5)-methyltransferase 3A, DNA MTase HsaIIIA, DNA methyltransferase HsaIIIA, DNMT3A2, Dnmt3a, ...
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Disease relevance of DNMT3A


High impact information on DNMT3A

  • Here we demonstrate that two recently identified DNA methyltransferases, Dnmt3a and Dnmt3b, are essential for de novo methylation and for mouse development [6].
  • Although enzymes have been identified that can methylate DNA de novo (Dnmt3a and Dnmt3b) (14), it is unknown how specific patterns of methylation are established in the genome [7].
  • Inactivation of both Dnmt3a and Dnmt3b, DNA methyltransferases essential for the initiation of de novo DNA methylation, abolished the establishment of DNA methylation and the silencing of Rhox cluster genes in the embryo proper [8].
  • Further, LANA associated with repressed cellular promoters, recruited Dnmt3a to DNA, and facilitated de novo promoter methylation of a down-regulated gene, cadherin 13 (H-cadherin) [4].
  • LANA preferentially relocalized Dnmt3a from the nuclear matrix into the chromatin fraction [4].

Chemical compound and disease context of DNMT3A


Biological context of DNMT3A


Anatomical context of DNMT3A


Associations of DNMT3A with chemical compounds

  • The importance of these Sp1-binding sites was demonstrated by using a GC-rich DNA-binding protein inhibitor, mithramycin A, i.e. on the basis of decrease in the promoter activities and mRNA expression levels of DNMT3A and DNMT3B [14].
  • Biochemical analysis revealed that whereas DNMT3L on its own does not significantly bind to the methyl group donor, S-adenosyl-L-methionine (SAM), it strongly increases the binding of SAM to DNMT3A2 [15].
  • Binding of DNMT3L to DNMT3A2 promotes a dramatic reorganization of DNMT3A2 subunits and leads to the formation of specific complexes with enhanced DNA methyltransferase activity and increased SAM binding [15].
  • Repair brings its own problems, since it will require remethylation of the replacement cytosine, presumably coupling repair to methylation by either the maintenance methylase Dnmt1 or a de novo enzyme such as Dnmt3a [16].
  • Analysis of the sites methylated in vivo using the bisulfite genomic sequencing method confirms the previous finding that some regions of the plasmid are much more methylated by Dnmt3a than other regions on the same plasmid [17].

Regulatory relationships of DNMT3A


Other interactions of DNMT3A


Analytical, diagnostic and therapeutic context of DNMT3A


  1. DNA hypomethylation and imbalanced expression of DNA methyltransferases (DNMT1, 3A, and 3B) in human uterine leiomyoma. Li, S., Chiang, T.C., Richard-Davis, G., Barrett, J.C., Mclachlan, J.A. Gynecol. Oncol. (2003) [Pubmed]
  2. Aberrant expression of deoxyribonucleic acid methyltransferases DNMT1, DNMT3A, and DNMT3B in women with endometriosis. Wu, Y., Strawn, E., Basir, Z., Halverson, G., Guo, S.W. Fertil. Steril. (2007) [Pubmed]
  3. Gene expression profiling identifies a set of transcripts that are up-regulated inhuman testicular seminoma. Yamada, S., Kohu, K., Ishii, T., Ishidoya, S., Ishidoya, S., Hiramatsu, M., Kanto, S., Fukuzaki, A., Adachi, Y., Endoh, M., Moriya, T., Sasaki, H., Satake, M., Arai, Y. DNA Res. (2004) [Pubmed]
  4. Recruitment of the de novo DNA methyltransferase Dnmt3a by Kaposi's sarcoma-associated herpesvirus LANA. Shamay, M., Krithivas, A., Zhang, J., Hayward, S.D. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
  5. A novel Dnmt3a isoform produced from an alternative promoter localizes to euchromatin and its expression correlates with active de novo methylation. Chen, T., Ueda, Y., Xie, S., Li, E. J. Biol. Chem. (2002) [Pubmed]
  6. DNA methyltransferases Dnmt3a and Dnmt3b are essential for de novo methylation and mammalian development. Okano, M., Bell, D.W., Haber, D.A., Li, E. Cell (1999) [Pubmed]
  7. Epigenetic reprogramming in mammalian development. Reik, W., Dean, W., Walter, J. Science (2001) [Pubmed]
  8. DNA methylation regulates long-range gene silencing of an X-linked homeobox gene cluster in a lineage-specific manner. Oda, M., Yamagiwa, A., Yamamoto, S., Nakayama, T., Tsumura, A., Sasaki, H., Nakao, K., Li, E., Okano, M. Genes Dev. (2006) [Pubmed]
  9. Physical and functional interaction of DNA methyltransferase 3A with Mbd3 and Brg1 in mouse lymphosarcoma cells. Datta, J., Majumder, S., Bai, S., Ghoshal, K., Kutay, H., Smith, D.S., Crabb, J.W., Jacob, S.T. Cancer Res. (2005) [Pubmed]
  10. Expression analysis of DNA methyltransferases 1, 3A, and 3B in sporadic breast carcinomas. Girault, I., Tozlu, S., Lidereau, R., Bièche, I. Clin. Cancer Res. (2003) [Pubmed]
  11. Cloning, expression and chromosome locations of the human DNMT3 gene family. Xie, S., Wang, Z., Okano, M., Nogami, M., Li, Y., He, W.W., Okumura, K., Li, E. Gene (1999) [Pubmed]
  12. Sex-specific windows for high mRNA expression of DNA methyltransferases 1 and 3A and methyl-CpG-binding domain proteins 2 and 4 in human fetal gonads. Galetzka, D., Weis, E., Tralau, T., Seidmann, L., Haaf, T. Mol. Reprod. Dev. (2007) [Pubmed]
  13. Expression of DNMT3A transcripts and nucleolar localization of DNMT3A protein in human testicular and fibroblast cells suggest a role for de novo DNA methylation in nucleolar inactivation. Galetzka, D., Tralau, T., Stein, R., Haaf, T. J. Cell. Biochem. (2006) [Pubmed]
  14. Transcriptional regulation of the human DNA methyltransferase 3A and 3B genes by Sp3 and Sp1 zinc finger proteins. Jinawath, A., Miyake, S., Yanagisawa, Y., Akiyama, Y., Yuasa, Y. Biochem. J. (2005) [Pubmed]
  15. Reconstitution and mechanism of the stimulation of de novo methylation by human DNMT3L. Kareta, M.S., Botello, Z.M., Ennis, J.J., Chou, C., Chédin, F. J. Biol. Chem. (2006) [Pubmed]
  16. Cytosine methylation and DNA repair. Walsh, C.P., Xu, G.L. Curr. Top. Microbiol. Immunol. (2006) [Pubmed]
  17. Murine de novo methyltransferase Dnmt3a demonstrates strand asymmetry and site preference in the methylation of DNA in vitro. Lin, I.G., Han, L., Taghva, A., O'Brien, L.E., Hsieh, C.L. Mol. Cell. Biol. (2002) [Pubmed]
  18. DNMT3L stimulates the DNA methylation activity of Dnmt3a and Dnmt3b through a direct interaction. Suetake, I., Shinozaki, F., Miyagawa, J., Takeshima, H., Tajima, S. J. Biol. Chem. (2004) [Pubmed]
  19. The DNA methyltransferase-like protein DNMT3L stimulates de novo methylation by Dnmt3a. Chedin, F., Lieber, M.R., Hsieh, C.L. Proc. Natl. Acad. Sci. U.S.A. (2002) [Pubmed]
  20. DNA methyltransferase-3a interacts with p53 and represses p53-mediated gene expression. Wang, Y.A., Kamarova, Y., Shen, K.C., Jiang, Z., Hahn, M.J., Wang, Y., Brooks, S.C. Cancer Biol. Ther. (2005) [Pubmed]
  21. CpG island hypermethylation in human colorectal tumors is not associated with DNA methyltransferase overexpression. Eads, C.A., Danenberg, K.D., Kawakami, K., Saltz, L.B., Danenberg, P.V., Laird, P.W. Cancer Res. (1999) [Pubmed]
  22. Role of DNA methyltransferases in regulation of human ribosomal RNA gene transcription. Majumder, S., Ghoshal, K., Datta, J., Smith, D.S., Bai, S., Jacob, S.T. J. Biol. Chem. (2006) [Pubmed]
  23. Dnmt3L is a transcriptional repressor that recruits histone deacetylase. Deplus, R., Brenner, C., Burgers, W.A., Putmans, P., Kouzarides, T., de Launoit, Y., Fuks, F. Nucleic Acids Res. (2002) [Pubmed]
  24. The histone methyltransferase SETDB1 and the DNA methyltransferase DNMT3A interact directly and localize to promoters silenced in cancer cells. Li, H., Rauch, T., Chen, Z.X., Szabó, P.E., Riggs, A.D., Pfeifer, G.P. J. Biol. Chem. (2006) [Pubmed]
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