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Dnmt1  -  DNA (cytosine-5-)-methyltransferase 1

Rattus norvegicus

Synonyms: DNA (cytosine-5)-methyltransferase 1, DNA MTase RnoIP, DNA methyltransferase I, M.RnoIP, MCMT
 
 
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High impact information on Dnmt1

  • Transfection of the gene encoding Dnmt1 induced morphological transformation, whereas inhibition of dnmt1 expression or activity resulted in reversion of fos transformation [1].
  • We report here that conditional gene deletion of the maintenance DNA methyltransferase I (Dnmt1) in neural progenitor cells (NPCs) results in DNA hypomethylation and precocious astroglial differentiation [2].
  • We propose that genome-wide and/or -specific local DNA methylation may be maintained by the Dnmt1-MeCP2 complexes, bound to hemimethylated DNA [3].
  • Here we show that the methyl-CpG binding protein, MeCP2, interacts directly with the maintenance DNA methyltransferase, Dnmt1 [3].
  • Transcription repression in oncogenic transformation: common targets of epigenetic repression in cells transformed by Fos, Ras or Dnmt1 [4].
 

Biological context of Dnmt1

  • Increased DNA (cytosine-5) methyltransferse (Dnmt1) activity is involved in the mechanism of transformation by both oncogenes, suggesting that inappropriate epigenetic transcription regulation may be a common route of oncogenesis, and that cell transformation may model aspects of the epigenetic deregulation that often occurs in tumors [4].
  • Here, we have taken a microarray-based gene expression approach to identify differentially expressed genes in cells transformed by c-fos, v-fos, ras or Dnmt1 [4].
  • We also found conserved cytoplasmic polyadenylation elements, usually implicated in regulating translation in oocytes, in Dnmt3b and Dnmt1 [5].
 

Anatomical context of Dnmt1

  • HT-29 cells cultured in the absence of selenium had significantly hypomethylated DNA but significantly more Dnmt1 protein expression than cells cultured in the presence of 1 or 2 micromol/L selenium [6].
  • We show that DNA methyltransferase (Dnmt1) activity is sharply reduced 4 days after induction of differentiation of PC12 cells with NGF [7].
  • At 1000x, the AhRM reduced Dnmt1 mRNA abundance to 28% and 32% of control in the liver and hypothalamus, respectively [8].
 

Associations of Dnmt1 with chemical compounds

  • We investigated changes in the DNA methylation machinery, namely, de novo DNA methyltransferases (Dnmt3a and 3b), maintenance DNA methyltransferase (Dnmt1), and methyl CpG binding proteins (MBDs), in rat livers during early stages of tumorigenesis [9].
  • The purpose of this study was to investigate whether the Dnmt1 inhibitor, 5-aza-2'-deoxycytidine (aza-dC) would alter the effect of dietary selenium on the formation of aberrant crypts [6].

References

  1. Role of DNA 5-methylcytosine transferase in cell transformation by fos. Bakin, A.V., Curran, T. Science (1999) [Pubmed]
  2. DNA methylation controls the timing of astrogliogenesis through regulation of JAK-STAT signaling. Fan, G., Martinowich, K., Chin, M.H., He, F., Fouse, S.D., Hutnick, L., Hattori, D., Ge, W., Shen, Y., Wu, H., ten Hoeve, J., Shuai, K., Sun, Y.E. Development (2005) [Pubmed]
  3. Methyl-CpG-binding protein, MeCP2, is a target molecule for maintenance DNA methyltransferase, Dnmt1. Kimura, H., Shiota, K. J. Biol. Chem. (2003) [Pubmed]
  4. Transcription repression in oncogenic transformation: common targets of epigenetic repression in cells transformed by Fos, Ras or Dnmt1. Ordway, J.M., Williams, K., Curran, T. Oncogene (2004) [Pubmed]
  5. Identification of 11 pseudogenes in the DNA methyltransferase gene family in rodents and humans and implications for the functional loci. Lees-Murdock, D.J., McLoughlin, G.A., McDaid, J.R., Quinn, L.M., O'Doherty, A., Hiripi, L., Hack, C.J., Walsh, C.P. Genomics (2004) [Pubmed]
  6. Dietary selenite and azadeoxycytidine treatments affect dimethylhydrazine-induced aberrant crypt formation in rat colon and DNA methylation in HT-29 cells. Davis, C.D., Uthus, E.O. J. Nutr. (2002) [Pubmed]
  7. Downregulation of DNA (cytosine-5-)methyltransferase is a late event in NGF-induced PC12 cell differentiation. Deng, J., Szyf, M. Brain Res. Mol. Brain Res. (1999) [Pubmed]
  8. Comparisons of brain, uterus, and liver mRNA expression for cytochrome p450s, DNA methyltransferase-1, and catechol-o-methyltransferase in prepubertal female Sprague-Dawley rats exposed to a mixture of aryl hydrocarbon receptor agonists. Desaulniers, D., Xiao, G.H., Leingartner, K., Chu, I., Musicki, B., Tsang, B.K. Toxicol. Sci. (2005) [Pubmed]
  9. A folate- and methyl-deficient diet alters the expression of DNA methyltransferases and methyl CpG binding proteins involved in epigenetic gene silencing in livers of F344 rats. Ghoshal, K., Li, X., Datta, J., Bai, S., Pogribny, I., Pogribny, M., Huang, Y., Young, D., Jacob, S.T. J. Nutr. (2006) [Pubmed]
 
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