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Gene Review

NDN  -  necdin, melanoma antigen (MAGE) family member

Homo sapiens

Synonyms: HsT16328, Necdin, PWCR
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Disease relevance of NDN


High impact information on NDN

  • Moreover, we found that CpG-rich regions in SNURF-SNRPN and NDN, which in somatic tissues are methylated on the maternal allele, are hypomethylated in unfertilized human oocytes [5].
  • The human necdin gene, NDN, is maternally imprinted and located in the Prader-Willi syndrome chromosomal region [6].
  • A complete lack of NDN expression in PWS brain and fibroblasts indicates that the gene is expressed exclusively from the paternal allele in these tissues and suggests a possible role of this new gene in PWS [6].
  • NDN displays several characteristics of an imprinted locus, including allelic DNA methylation and asynchronous DNA replication [6].
  • By using a yeast two-hybrid method, we found that pre-IL-1 alpha binds necdin, a nuclear protein with growth suppressor activity [7].

Chemical compound and disease context of NDN


Biological context of NDN


Anatomical context of NDN


Associations of NDN with chemical compounds

  • We also found that NDN lies in a domain of paternal allele-specific histone hyperacetylation that correlates with transcriptional state, and a domain of differential histone H3 lysine 4 di- and tri-methylation that persists independent of transcription [8].
  • Necdin and E2F4 are modulated by rosiglitazone therapy in diabetic human adipose and muscle tissue [10].
  • Necdin enhanced the cytoplasmic retention of NEFA-GFP and potentiated the effect of NEFA-GFP on caffeine-evoked elevation of cytosolic Ca(2+) levels [2].
  • Thyroid hormone-mediated negative transcriptional regulation of Necdin expression [9].

Physical interactions of NDN


Regulatory relationships of NDN

  • The necdin gene is expressed predominantly in postmitotic neurons and encodes a growth suppressor that interacts with the transcription factors E2F1 and p53 [1].
  • Based on these findings, we propose that the constitutively up-regulated expression of pre-IL-1 alpha in the nuclei of SSc fibroblasts up-regulates proliferation and matrix production of SSc fibroblasts through binding necdin, and by counteracting its effects on cell growth and collagen production [7].
  • These results suggest that necdin suppresses cell proliferation through its interaction with hnRNP U in the specific subnuclear structure [14].

Other interactions of NDN


Analytical, diagnostic and therapeutic context of NDN

  • Necdin significantly increased the populations of cells expressing the GABAergic neuron markers calbindin D-28k and glutamic acid decarboxylase when overexpressed by electroporation in cultured forebrain slices [12].
  • The orthologous mouse gene (Magel2) is located within 150 kb of NDN:, is imprinted with paternal-only expression and is expressed predominantly in late developmental stages and adult brain as shown by northern blotting, RT-PCR and whole-mount RNA in situ hybridization [13].
  • We have now examined the chromatin accessibility of the promoter region of one of the Imprinting Centre-controlled genes, NDN encoding necdin, using in vivo DNA footprinting to identify sites of DNA-protein interaction and altered chromatin configuration [18].


  1. Characterization and chromosomal mapping of a human Necdin pseudogene. Nakada, Y., Taniura, H., Uetsuki, T., Yoshikawa, K. Gene (2000) [Pubmed]
  2. The postmitotic growth suppressor necdin interacts with a calcium-binding protein (NEFA) in neuronal cytoplasm. Taniguchi, N., Taniura, H., Niinobe, M., Takayama, C., Tominaga-Yoshino, K., Ogura, A., Yoshikawa, K. J. Biol. Chem. (2000) [Pubmed]
  3. Functional domains of necdin for protein-protein interaction, nuclear matrix targeting, and cell growth suppression. Taniura, H., Kobayashi, M., Yoshikawa, K. J. Cell. Biochem. (2005) [Pubmed]
  4. Systematic screening for mutations in the human necdin gene (NDN): identification of two naturally occurring polymorphisms and association analysis in body weight regulation. Oeffner, F., Korn, T., Roth, H., Ziegler, A., Hinney, A., Goldschmidt, H., Siegfried, W., Hebebrand, J., Grzeschik, K.H. Int. J. Obes. Relat. Metab. Disord. (2001) [Pubmed]
  5. Maternal methylation imprints on human chromosome 15 are established during or after fertilization. El-Maarri, O., Buiting, K., Peery, E.G., Kroisel, P.M., Balaban, B., Wagner, K., Urman, B., Heyd, J., Lich, C., Brannan, C.I., Walter, J., Horsthemke, B. Nat. Genet. (2001) [Pubmed]
  6. The human necdin gene, NDN, is maternally imprinted and located in the Prader-Willi syndrome chromosomal region. Jay, P., Rougeulle, C., Massacrier, A., Moncla, A., Mattei, M.G., Malzac, P., Roëckel, N., Taviaux, S., Lefranc, J.L., Cau, P., Berta, P., Lalande, M., Muscatelli, F. Nat. Genet. (1997) [Pubmed]
  7. A nuclear target for interleukin-1alpha: interaction with the growth suppressor necdin modulates proliferation and collagen expression. Hu, B., Wang, S., Zhang, Y., Feghali, C.A., Dingman, J.R., Wright, T.M. Proc. Natl. Acad. Sci. U.S.A. (2003) [Pubmed]
  8. Tissue-specific and imprinted epigenetic modifications of the human NDN gene. Lau, J.C., Hanel, M.L., Wevrick, R. Nucleic Acids Res. (2004) [Pubmed]
  9. Thyroid hormone-mediated negative transcriptional regulation of Necdin expression. Nygård, M., Becker, N., Demeneix, B., Pettersson, K., Bondesson, M. J. Mol. Endocrinol. (2006) [Pubmed]
  10. Necdin and E2F4 are modulated by rosiglitazone therapy in diabetic human adipose and muscle tissue. Goldfine, A.B., Crunkhorn, S., Costello, M., Gami, H., Landaker, E.J., Niinobe, M., Yoshikawa, K., Lo, D., Warren, A., Jimenez-Chillaron, J., Patti, M.E. Diabetes (2006) [Pubmed]
  11. The necdin gene is deleted in Prader-Willi syndrome and is imprinted in human and mouse. MacDonald, H.R., Wevrick, R. Hum. Mol. Genet. (1997) [Pubmed]
  12. Necdin promotes GABAergic neuron differentiation in cooperation with Dlx homeodomain proteins. Kuwajima, T., Nishimura, I., Yoshikawa, K. J. Neurosci. (2006) [Pubmed]
  13. Expression and imprinting of MAGEL2 suggest a role in Prader-willi syndrome and the homologous murine imprinting phenotype. Lee, S., Kozlov, S., Hernandez, L., Chamberlain, S.J., Brannan, C.I., Stewart, C.L., Wevrick, R. Hum. Mol. Genet. (2000) [Pubmed]
  14. Necdin interacts with the ribonucleoprotein hnRNP U in the nuclear matrix. Taniura, H., Yoshikawa, K. J. Cell. Biochem. (2002) [Pubmed]
  15. Multipoint imprinting analysis in sporadic colorectal cancers with and without microsatellite instability. Nishihara, S., Hayashida, T., Mitsuya, K., Schulz, T.C., Ikeguchi, M., Kaibara, N., Oshimura, M. Int. J. Oncol. (2000) [Pubmed]
  16. Cancer/testis antigens: structural and immunobiological properties. Kirkin, A.F., Dzhandzhugazyan, K.N., Zeuthen, J. Cancer Invest. (2002) [Pubmed]
  17. The MAGE proteins: emerging roles in cell cycle progression, apoptosis, and neurogenetic disease. Barker, P.A., Salehi, A. J. Neurosci. Res. (2002) [Pubmed]
  18. Chromatin modification of the human imprinted NDN (necdin) gene detected by in vivo footprinting. Hanel, M.L., Lau, J.C., Paradis, I., Drouin, R., Wevrick, R. J. Cell. Biochem. (2005) [Pubmed]
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