The world's first wiki where authorship really matters (Nature Genetics, 2008). Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts. Search thousands of articles and collaborate with scientists around the globe.

wikigene or wiki gene protein drug chemical gene disease author authorship tracking collaborative publishing evolutionary knowledge reputation system wiki2.0 global collaboration genes proteins drugs chemicals diseases compound
Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)



Gene Review

Dlk1  -  delta-like 1 homolog (Drosophila)

Mus musculus

Synonyms: AW742678, Adipocyte differentiation inhibitor protein, DLK-1, Dlk, DlkI, ...
Welcome! If you are familiar with the subject of this article, you can contribute to this open access knowledge base by deleting incorrect information, restructuring or completely rewriting any text. Read more.

Disease relevance of Dlk1


High impact information on Dlk1

  • Here we report the cloning of new complementary DNAs that encode the 3T3 preadipocyte factor (termed AEBP1) and demonstrate that AEBP1 expression is abolished during adipocyte differentiation [4].
  • Furthermore, we show that Dlk1 is tightly linked to the maternally expressed Gtl2 gene [5].
  • In preadipocytes Foxa-2 inhibits adipocyte differentiation by activating transcription of the Pref-1 gene [6].
  • These findings demonstrate the inhibition of adipogenesis by Pref-1 in vivo and the resulting impairment of adipocyte function that leads to the development of metabolic abnormalities [1].
  • Mice expressing the Pref-1/hFc transgene exclusively in liver under the control of the albumin promoter also showed a decrease in adipose mass and adipocyte marker expression, suggesting an endocrine mode of action of Pref-1 [1].

Biological context of Dlk1


Anatomical context of Dlk1


Associations of Dlk1 with chemical compounds


Regulatory relationships of Dlk1

  • TNF alpha-mediated inhibition and reversal of adipocyte differentiation is accompanied by suppressed expression of PPARgamma without effects on Pref-1 expression [16].
  • These results indicate that Pref-1 expressed by TE cells and HES-1 expressed by thymocytes are critically involved in supporting thymocyte cellularity [17].

Other interactions of Dlk1

  • The imprinted Dlk1-Dio3 region on mouse chromosome 12 contains six imprinted genes and a number of maternally expressed snoRNAs and miRNAs [18].
  • We show that the two genes located immediately proximal to Dlk1, the Yy1 and Wars genes, are expressed in a biallelic manner [19].
  • Imprinting of Igf2r, Kcnq1, Gt12, and Dlk1 varied among individuals [20].
  • Dlk was expressed exclusively from the paternal allele in both the embryo and placenta, but the CpG-island promoter of Dlk was completely unmethylated on both parental alleles [21].
  • Insulin-like growth factor-1/insulin bypasses Pref-1/FA1-mediated inhibition of adipocyte differentiation [12].

Analytical, diagnostic and therapeutic context of Dlk1

  • Assignment of dlk (Dlk1) to mouse chromosome band 12E-F1 by in situ hybridization [22].
  • In addition, coculture of C3H10T1/2 cells with other cells expressing Dlk1, but not with cells lacking Dlk1 expression, enhances their adipogenic response [9].
  • We have used BAC transgenesis in the mouse to begin to delineate the region of DNA required for proper expression and imprinting of the mouse Delta-like1 (Dlk1) and Gene-trap locus2 (Gtl2) imprinted genes [23].
  • By transplantation of Dlk+ cells into the spleen, donor-derived hepatocytes were found in the recipient liver, indicating that Dlk+ cells differentiated into hepatocytes in vivo [11].
  • Through RT-PCR and the isolation and analysis of multiple pref-1 cDNA clones, we have identified, in addition to full-length pref-1, five alternately spliced forms with various in-frame deletions of all or a part of the sixth EGF-like repeat, juxta-membrane, and predicted transmembrane domains.(ABSTRACT TRUNCATED AT 250 WORDS)[24]


  1. Inhibition of adipogenesis and development of glucose intolerance by soluble preadipocyte factor-1 (Pref-1). Lee, K., Villena, J.A., Moon, Y.S., Kim, K.H., Lee, S., Kang, C., Sul, H.S. J. Clin. Invest. (2003) [Pubmed]
  2. Mice lacking paternally expressed Pref-1/Dlk1 display growth retardation and accelerated adiposity. Moon, Y.S., Smas, C.M., Lee, K., Villena, J.A., Kim, K.H., Yun, E.J., Sul, H.S. Mol. Cell. Biol. (2002) [Pubmed]
  3. UM-SCP-1, a new human cell line derived from a prostatic squamous cell carcinoma. Grossman, H.B., Wedemeyer, G., Ren, L., Carey, T.E. Cancer Res. (1984) [Pubmed]
  4. A eukaryotic transcriptional repressor with carboxypeptidase activity. He, G.P., Muise, A., Li, A.W., Ro, H.S. Nature (1995) [Pubmed]
  5. The Dlk1 and Gtl2 genes are linked and reciprocally imprinted. Schmidt, J.V., Matteson, P.G., Jones, B.K., Guan, X.J., Tilghman, S.M. Genes Dev. (2000) [Pubmed]
  6. Role of Foxa-2 in adipocyte metabolism and differentiation. Wolfrum, C., Shih, D.Q., Kuwajima, S., Norris, A.W., Kahn, C.R., Stoffel, M. J. Clin. Invest. (2003) [Pubmed]
  7. Epigenetic analysis of the Dlk1-Gtl2 imprinted domain on mouse chromosome 12: implications for imprinting control from comparison with Igf2-H19. Takada, S., Paulsen, M., Tevendale, M., Tsai, C.E., Kelsey, G., Cattanach, B.M., Ferguson-Smith, A.C. Hum. Mol. Genet. (2002) [Pubmed]
  8. DNA methylation imprints on the IG-DMR of the Dlk1-Gtl2 domain in mouse male germline. Hiura, H., Komiyama, J., Shirai, M., Obata, Y., Ogawa, H., Kono, T. FEBS Lett. (2007) [Pubmed]
  9. The EGF-like Protein dlk1 Inhibits Notch Signaling and Potentiates Adipogenesis of Mesenchymal Cells. Nueda, M.L., Baladrón, V., Sánchez-Solana, B., Ballesteros, M.A., Laborda, J. J. Mol. Biol. (2007) [Pubmed]
  10. Wnt-4 deficiency alters mouse adrenal cortex function, reducing aldosterone production. Heikkilä, M., Peltoketo, H., Leppäluoto, J., Ilves, M., Vuolteenaho, O., Vainio, S. Endocrinology (2002) [Pubmed]
  11. Isolation of hepatoblasts based on the expression of Dlk/Pref-1. Tanimizu, N., Nishikawa, M., Saito, H., Tsujimura, T., Miyajima, A. J. Cell. Sci. (2003) [Pubmed]
  12. Insulin-like growth factor-1/insulin bypasses Pref-1/FA1-mediated inhibition of adipocyte differentiation. Zhang, H., Nøohr, J., Jensen, C.H., Petersen, R.K., Bachmann, E., Teisner, B., Larsen, L.K., Mandrup, S., Kristiansen, K. J. Biol. Chem. (2003) [Pubmed]
  13. Adenomyosis--a result of disordered stromal differentiation. Parrott, E., Butterworth, M., Green, A., White, I.N., Greaves, P. Am. J. Pathol. (2001) [Pubmed]
  14. Regulation of preadipocyte factor-1 gene expression during 3T3-L1 cell differentiation. Boney, C.M., Fiedorek, F.T., Paul, S.R., Gruppuso, P.A. Endocrinology (1996) [Pubmed]
  15. Only the large soluble form of preadipocyte factor-1 (Pref-1), but not the small soluble and membrane forms, inhibits adipocyte differentiation: role of alternative splicing. Mei, B., Zhao, L., Chen, L., Sul, H.S. Biochem. J. (2002) [Pubmed]
  16. TNF alpha-mediated inhibition and reversal of adipocyte differentiation is accompanied by suppressed expression of PPARgamma without effects on Pref-1 expression. Xing, H., Northrop, J.P., Grove, J.R., Kilpatrick, K.E., Su, J.L., Ringold, G.M. Endocrinology (1997) [Pubmed]
  17. A role for pref-1 and HES-1 in thymocyte development. Kaneta, M., Osawa, M., Sudo, K., Nakauchi, H., Farr, A.G., Takahama, Y. J. Immunol. (2000) [Pubmed]
  18. High-resolution map and imprinting analysis of the Gtl2-Dnchc1 domain on mouse chromosome 12. Tierling, S., Dalbert, S., Schoppenhorst, S., Tsai, C.E., Oliger, S., Ferguson-Smith, A.C., Paulsen, M., Walter, J. Genomics (2006) [Pubmed]
  19. Analysis of candidate imprinted genes linked to Dlk1-Gtl2 using a congenic mouse line. Yevtodiyenko, A., Carr, M.S., Patel, N., Schmidt, J.V. Mamm. Genome (2002) [Pubmed]
  20. Increased plasticity of genomic imprinting of Dlk1 in brain is due to genetic and epigenetic factors. Croteau, S., Roquis, D., Charron, M.C., Frappier, D., Yavin, D., Loredo-Osti, J.C., Hudson, T.J., Naumova, A.K. Mamm. Genome (2005) [Pubmed]
  21. Delta-like and gtl2 are reciprocally expressed, differentially methylated linked imprinted genes on mouse chromosome 12. Takada, S., Tevendale, M., Baker, J., Georgiades, P., Campbell, E., Freeman, T., Johnson, M.H., Paulsen, M., Ferguson-Smith, A.C. Curr. Biol. (2000) [Pubmed]
  22. Assignment of dlk (Dlk1) to mouse chromosome band 12E-F1 by in situ hybridization. Gubina, E., Ruiz-Hidalgo, M.J., Baladrón, V., Laborda, J. Cytogenet. Cell Genet. (2000) [Pubmed]
  23. A 178-kb BAC transgene imprints the mouse Gtl2 gene and localizes tissue-specific regulatory elements. Yevtodiyenko, A., Steshina, E.Y., Farner, S.C., Levorse, J.M., Schmidt, J.V. Genomics (2004) [Pubmed]
  24. Structural characterization and alternate splicing of the gene encoding the preadipocyte EGF-like protein pref-1. Smas, C.M., Green, D., Sul, H.S. Biochemistry (1994) [Pubmed]
WikiGenes - Universities