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Hnmt  -  histamine N-methyltransferase

Mus musculus

Synonyms: 1500031F01Rik, AI788969, HMT, Histamine N-methyltransferase, Hmt
 
 
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Disease relevance of Hnmt

  • Cloudman (S91) murine melanoma cells were treated with 4'-hydroxymethyltrioxsalen (HMT), a bifunctional psoralen and exposed to long-wavelength (365 nm) ultraviolet light [1].
  • Isolation of HPRT deficient clones has permitted a molecular characterization of the mutational pattern induced by the photosensitization reaction mediated by HMT [2].
  • In addition, the change in HMT activity in MRL/l mice treated with corticosteroid appeared earlier than changes in clinicopathological examinations including skin eruptions, dermatopathology and proteinuria [3].
  • The effects of the reaction photosensitized by 4'-hydroxymethyl-4,5'-8-trimethylpsoralen (HMT) on a mouse lymphoma cell line have been examined [2].
  • Pathogenesis of lupus dermatoses in autoimmune mice. X. Evaluation of histamine-N-methyltransferase activity in the skin of autoimmune [3].
 

Psychiatry related information on Hnmt

 

High impact information on Hnmt

  • Suv39h1 is a histone H3 lysine-9 (H3-K9) specific methyltransferase (HMT) that is associated with gene silencing through chromatin modification [5].
  • Increased Suv39h1 expression repressed MyoD-dependent muscle gene expression and this property required its HMT activity [5].
  • H-2M3 encodes HMT, the major histocompatibility complex (MHC) class I heavy chain of the maternally transmitted antigen (Mta) [6].
  • Here we show for the first time that histone methylation occurs in both the germ cells and somatic cells of the Drosophila ovary, and demonstrate in vivo that an HMT, the product of the eggless (egg) gene, is required for oogenesis [7].
  • In conclusion, we have shown that extremely sparse substitution of HMT to DNA blocks melanoma cells in the G2 phase or other phases of the cell cycle in a dose-dependent manner [1].
 

Biological context of Hnmt

  • The mouse HNMT gene, Hnmt, spanned approximately 25 kb and had 7 exons [8].
  • Hnmt mapped to mouse chromosome 2 in an area of conserved synteny to human chromosome 2q, the location of the human gene (2q22) on the basis of fluorescence in situ hybridization [8].
  • Marked sequence similarities between rat and mouse introns were present near splice sites and outside the junction residues, suggesting the evolutionary relationship between the structural features of the rat and mouse HMT genes [9].
  • CONCLUSIONS: Cloning and functional characterization of the mouse HNMT cDNA and gene will now make it possible to study in the mouse molecular genetic mechanisms involved the regulation of this important histamine-metabolizing enzyme [8].
  • RESULTS: The mouse liver HNMT cDNA was 1657 bp in length with an 888 bp open reading frame (ORF) that encoded a 296 amino acid protein with a predicted Mr value of approximately 32.5 kDa [8].
 

Anatomical context of Hnmt

  • Mouse HNMT was expressed in COS-1 cells, and its apparent Km values for histamine and S-adenosyl-L-methionine (Ado-Met), the two cosubstrates for the reaction, were 5.3 and 5.8 microM, respectively [8].
  • In search of novel ways to enhance histaminergic neurotransmission in the central nervous system, a new class of nonimidazole histamine H(3) receptor ligands were developed that simultaneously possess strong inhibitory activity on the main histamine metabolizing enzyme, histamine N-methyltransferase (HMT) [10].
  • These results show that Mta and Qa1b, although affected, are not obliterated by the defect in RMA-S cells; that the association of MTF peptides with HMT is exclusive; and that MTF enters the endoplasmic reticulum in the same fashion as other endogenous peptides [11].
  • To test whether HMT activity influences euchromatic cytosine methylation, we analyzed the DNA methylation status of approximately 2000 CpG-rich loci, which are predicted in silico, in G9a(-/-) embryonic stem cells by restriction landmark genomic scanning (RLGS) [12].
  • AT decreases ability of synaptosomes to actively accumulate HA precursor, L-[U-14C]histidine, measured after rapid centrifugation of synaptosomes through silicone oil, as well as lowers activity of HA catabolizing enzyme histamine N-methyltransferase (by 57%) [13].
 

Associations of Hnmt with chemical compounds

 

Analytical, diagnostic and therapeutic context of Hnmt

References

  1. Dose-related effects of psoralen and ultraviolet light on the cell cycle of murine melanoma cells. Varga, J.M., Wiesehahn, G., Bartholomew, J.C., Hearst, J.E. Cancer Res. (1982) [Pubmed]
  2. Molecular analysis of mutations induced by 4'-hydroxymethyl-4,5',8-trimethylpsoralen and UVA in the mouse HPRT gene. Piette, J. J. Photochem. Photobiol. B, Biol. (1992) [Pubmed]
  3. Pathogenesis of lupus dermatoses in autoimmune mice. X. Evaluation of histamine-N-methyltransferase activity in the skin of autoimmune. Furukawa, F., Taniguchi, S., Tachibana, T., Horiguchi, Y., Kanauchi, H., Ohshio, G., Hamashima, Y., Imamura, S. Microbiol. Immunol. (1988) [Pubmed]
  4. Effects of (S)-alpha -fluoromethylhistidine and metoprine on locomotor activity and brain histamine content in mice. Sakai, N., Onodera, K., Maeyama, K., Yanai, K., Watanabe, T. Life Sci. (1992) [Pubmed]
  5. Histone methyltransferase Suv39h1 represses MyoD-stimulated myogenic differentiation. Mal, A.K. EMBO J. (2006) [Pubmed]
  6. HMT, encoded by H-2M3, is a neoclassical major histocompatibility class I antigen. Wang, C.R., Lindahl, K.F. Proc. Natl. Acad. Sci. U.S.A. (1993) [Pubmed]
  7. Histone methylation is required for oogenesis in Drosophila. Clough, E., Moon, W., Wang, S., Smith, K., Hazelrigg, T. Development (2007) [Pubmed]
  8. Mouse histamine N-methyltransferase: cDNA cloning, expression, gene cloning and chromosomal localization. Wang, L., Yan, L., McGuire, C., Kozak, C.A., Wang, M., Kim, U.J., Siciliano, M., Weinshilboum, R.M. Inflamm. Res. (2001) [Pubmed]
  9. Genomic structure of the rat and mouse histamine N-methyltransferase gene. Kitanaka, N., Kitanaka, J., Oue, T., Tada, Y., Tanaka, T., Takemura, M. Jpn. J. Pharmacol. (2002) [Pubmed]
  10. Development of a new class of nonimidazole histamine H(3) receptor ligands with combined inhibitory histamine N-methyltransferase activity. Apelt, J., Ligneau, X., Pertz, H.H., Arrang, J.M., Ganellin, C.R., Schwartz, J.C., Schunack, W., Stark, H. J. Med. Chem. (2002) [Pubmed]
  11. Expression of medial class I histocompatibility antigens on RMA-S mutant cells. Hermel, E., Grigorenko, E., Lindahl, K.F. Int. Immunol. (1991) [Pubmed]
  12. Genome-wide and locus-specific DNA hypomethylation in G9a deficient mouse embryonic stem cells. Ikegami, K., Iwatani, M., Suzuki, M., Tachibana, M., Shinkai, Y., Tanaka, S., Greally, J.M., Yagi, S., Hattori, N., Shiota, K. Genes Cells (2007) [Pubmed]
  13. Effect of in vivo glucocorticoid administration on histamine metabolism in rat brain synaptosomes. Wałajtys-Rode, E., Waśkiewicz, J., Rafałowska, U. Neurosci. Lett. (1989) [Pubmed]
  14. Decreased transmethylation of biogenic amines after in vivo elevation of brain S-adenosyl-l-homocysteine. Schatz, R.A., Wilens, T.E., Sellinger, O.Z. J. Neurochem. (1981) [Pubmed]
  15. Effect of reserpine on histamine metabolism in the mouse brain. Muroi, N., Oishi, R., Saeki, K. J. Pharmacol. Exp. Ther. (1991) [Pubmed]
  16. Possible role of increased brain methylation in methionine sulfoximine epileptogenesis: effects of administration of adenosine and homocysteine thiolactone. Schatz, R.A., Wilens, T.E., Tatter, S.B., Gregor, P., Sellinger, O.Z. J. Neurosci. Res. (1983) [Pubmed]
  17. Effects of two histamine-N-methyltransferase inhibitors, SKF 91488 and BW 301 U, in rodent antinociception. Malmberg-Aiello, P., Lamberti, C., Ipponi, A., Hänninen, J., Ghelardini, C., Bartolini, A. Naunyn Schmiedebergs Arch. Pharmacol. (1997) [Pubmed]
  18. Inhibition of histamine versus acetylcholine metabolism as a mechanism of tacrine activity. Morisset, S., Traiffort, E., Schwartz, J.C. Eur. J. Pharmacol. (1996) [Pubmed]
  19. 9-Amino-1,2,3,4-tetrahydroacridine is a potent inhibitor of histamine N-methyltransferase. Nishibori, M., Oishi, R., Itoh, Y., Saeki, K. Jpn. J. Pharmacol. (1991) [Pubmed]
 
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