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Gene Review

Hoxc8  -  homeobox C8

Mus musculus

Synonyms: D130011F21Rik, Homeobox protein Hox-3.1, Homeobox protein Hox-C8, Homeobox protein M31, Hox-3.1, ...
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Disease relevance of Hoxc8

  • Analysis of plausible downstream target genes of Hoxc8 in F9 teratocarcinoma cells. Putative downstream target genes of Hoxc8 [1].
  • We previously reported that overexpression of the homeobox genes Hoxc8 and Hoxd4 results in severe cartilage defects, reduced proteoglycan content, accumulation of immature chondrocytes, and decreased maturation to hypertrophy [2].
  • The SV40 DNA retained in M31 is colinear with SV40 virion DNA, and a unit length of SV40 DNA was deleted within the SV40 sequences present in W-2K-11 cells [3].
  • Simian virus 40 (SV40) DNA insertions from SV40-transformed mouse cell line W-2K-11 and its revertants M18, M31, and M42 were cloned [3].
  • The baculovirus expression system was employed to demonstrate that Hoxb-6 is phosphorylated in Sf9 cells while Hoxc-8 is not [4].

High impact information on Hoxc8


Biological context of Hoxc8

  • The transcriptional regulation of the Hoxc8 gene is controlled during early mouse embryogenesis by an enhanceosome-like control region, termed the early enhancer (EE), located 3 kb upstream from the Hoxc8 translation start site [8].
  • The phenotype of Hoxd8 loss-of-function mutants is presented, and compared with that of Hoxb8- and Hoxc8-null mice [9].
  • The Hoxc8 expression first appears in skin at 14.5 days of gestation in the sternal region and is extended at 16.5 days to the thoracic ventral and lumbar dorsal regions [10].
  • Divergence of Hoxc8 early enhancer parallels diverged axial morphologies between mammals and fishes [11].
  • Extensive restructuring of the Hoxc8 early enhancer including nucleotide substitutions, inversion, and divergence result in distinct patterns of reporter gene expression along the embryonic axis [11].

Anatomical context of Hoxc8


Associations of Hoxc8 with chemical compounds


Regulatory relationships of Hoxc8


Other interactions of Hoxc8

  • 5. In contrast to Hox-3.1, Hox-3.2 is not expressed in the dorsal horns containing the sensory neurons at day 14.5 p.c. Hox-3.2 transcripts are also detected in the posterior prevertebrae, the hindlimb buds and the cortex of the developing kidney [19].
  • In the mouse, Llglh is thought to play an important role during brain development as a regulatory target of Hoxc8 [20].
  • The expression domains of Hoxa-7, Hoxc-8, and Hoxc-9 genes as examined by whole mount in situ hybridization were found to be shifted anteriorly in heated embryos [21].
  • Restriction endonuclease fragment length variations (RFLV) were detected by use of the cDNA probe Hox-3.1 for the homeo box-3.1 gene and also the c-myc oncogene probe for exon 2 [22].
  • The molecular basis of the Raldh2L-/- phenotype relies in part on the deregulation of Hoxc8, which in turn regulates the RA receptor RARbeta [14].

Analytical, diagnostic and therapeutic context of Hoxc8

  • Chromatin immunoprecipitation experiments reveal that menin is bound to the Hoxc8 locus [23].
  • The Hoxc8 expression pattern was examined in mouse embryos 7.5-12.5 days postcoitum (dpc) using whole-mount in situ hybridization and RT-PCR [24].
  • Quantitative real-time PCR was performed on cDNA samples derived from RNA isolated from primary chondrocytes of individual rib cartilages from Hoxd4 and Hoxc8 transgenic mice, respectively [2].
  • Sequence analysis of the 5' region of the Hox-3.1 gene extending to its nearest upstream neighbor, Hox-3.2, allowed us to identify sequences known to be capable of interactions with transcription factors [25].
  • Most important, using a high throughput screening assay based on mimicking Smad1C's displacement of Hoxc-8 binding to DNA, we identified chemical entities that exhibit bone anabolic activity in cell and bone organ cultures, suggesting the possibility that the compounds may be used as bone anabolic agents to treat bone pathologies [26].


  1. Analysis of plausible downstream target genes of Hoxc8 in F9 teratocarcinoma cells. Putative downstream target genes of Hoxc8. Kwon, Y., Ko, J.H., Byung-Gyu, K., Kim, M.H., Kim, B. Mol. Biol. Rep. (2003) [Pubmed]
  2. Expression of folate pathway genes in the cartilage of Hoxd4 and Hoxc8 transgenic mice. Kruger, C., Talmadge, C., Kappen, C. Birth Defects Res. Part A Clin. Mol. Teratol. (2006) [Pubmed]
  3. Two types of deletion within integrated viral sequences mediate reversion of simian virus 40-transformed mouse cells. Maruyama, K., Oda, K. J. Virol. (1984) [Pubmed]
  4. Phylogenetically conserved CK-II phosphorylation site of the murine homeodomain protein Hoxb-6. Fienberg, A.A., Nordstedt, C., Belting, H.G., Czernik, A.J., Nairn, A.C., Gandy, S., Greengard, P., Ruddle, F.H. J. Exp. Zool. (1999) [Pubmed]
  5. Region-specific expression of two mouse homeo box genes. Utset, M.F., Awgulewitsch, A., Ruddle, F.H., McGinnis, W. Science (1987) [Pubmed]
  6. Pattern of transcription of the homeo gene Hox-3.1 in the mouse embryo. Le Mouellic, H., Condamine, H., Brûlet, P. Genes Dev. (1988) [Pubmed]
  7. Primary structure and developmental expression pattern of Hox 3.1, a member of the murine Hox 3 homeobox gene cluster. Breier, G., Dressler, G.R., Gruss, P. EMBO J. (1988) [Pubmed]
  8. Isolation and characterization of BEN, a member of the TFII-I family of DNA-binding proteins containing distinct helix-loop-helix domains. Bayarsaihan, D., Ruddle, F.H. Proc. Natl. Acad. Sci. U.S.A. (2000) [Pubmed]
  9. Axial skeletal patterning in mice lacking all paralogous group 8 Hox genes. van den Akker, E., Fromental-Ramain, C., de Graaff, W., Le Mouellic, H., Brûlet, P., Chambon, P., Deschamps, J. Development (2001) [Pubmed]
  10. Differential expression of two different homeobox gene families during mouse tegument morphogenesis. Kanzler, B., Viallet, J.P., Le Mouellic, H., Boncinelli, E., Duboule, D., Dhouailly, D. Int. J. Dev. Biol. (1994) [Pubmed]
  11. Divergence of Hoxc8 early enhancer parallels diverged axial morphologies between mammals and fishes. Anand, S., Wang, W.C., Powell, D.R., Bolanowski, S.A., Zhang, J., Ledje, C., Pawashe, A.B., Amemiya, C.T., Shashikant, C.S. Proc. Natl. Acad. Sci. U.S.A. (2003) [Pubmed]
  12. Modification of expression and cis-regulation of Hoxc8 in the evolution of diverged axial morphology. Belting, H.G., Shashikant, C.S., Ruddle, F.H. Proc. Natl. Acad. Sci. U.S.A. (1998) [Pubmed]
  13. The identification of Hoxc8 target genes. Lei, H., Wang, H., Juan, A.H., Ruddle, F.H. Proc. Natl. Acad. Sci. U.S.A. (2005) [Pubmed]
  14. Retinaldehyde dehydrogenase 2 and Hoxc8 are required in the murine brachial spinal cord for the specification of Lim1+ motoneurons and the correct distribution of Islet1+ motoneurons. Vermot, J., Schuhbaur, B., Le Mouellic, H., McCaffery, P., Garnier, J.M., Hentsch, D., Brûlet, P., Niederreither, K., Chambon, P., Dollé, P., Le Roux, I. Development (2005) [Pubmed]
  15. A chicken genomic DNA fragment that hybridizes to the murine Hox-3.1 homeobox is likely to encode the NADH ubiquinone oxidoreductase subunit B15. Goldberg, G.S., Kaczmarczyk, W. Gene (1993) [Pubmed]
  16. Hoxc-9 mutant mice show anterior transformation of the vertebrae and malformation of the sternum and ribs. Suemori, H., Takahashi, N., Noguchi, S. Mech. Dev. (1995) [Pubmed]
  17. Repression of the beta-amyloid gene in a Hox-3.1-producing cell line. Violette, S.M., Shashikant, C.S., Salbaum, J.M., Belting, H.G., Wang, J.C., Ruddle, F.H. Proc. Natl. Acad. Sci. U.S.A. (1992) [Pubmed]
  18. An induction gene trap for identifying a homeoprotein-regulated locus. Mainguy, G., Montesinos, M.L., Lesaffre, B., Zevnik, B., Karasawa, M., Kothary, R., Wurst, W., Prochiantz, A., Volovitch, M. Nat. Biotechnol. (2000) [Pubmed]
  19. Structure and expression pattern of the murine Hox-3.2 gene. Erselius, J.R., Goulding, M.D., Gruss, P. Development (1990) [Pubmed]
  20. The human homologue of the murine Llglh gene (LLGL) maps within the Smith-Magenis syndrome region in 17p11.2. Koyama, K., Fukushima, Y., Inazawa, J., Tomotsune, D., Takahashi, N., Nakamura, Y. Cytogenet. Cell Genet. (1996) [Pubmed]
  21. Heat shock-induced homeotic transformations of the axial skeleton and associated shifts of Hox gene expression domains in mouse embryos. Li, Z.L., Chisaka, O., Koseki, H., Akasaka, T., Ishibashi, M., Shiota, K. Reprod. Toxicol. (1997) [Pubmed]
  22. Mapping of the Hox-3.1 and Myc-1.2 genes on chromosome 15 of the mouse by restriction fragment length variations. Watanabe, T., Ohno, K., Shimizu, A., Sakai, Y., Takahashi, M., Takahashi, N. Biochem. Genet. (1990) [Pubmed]
  23. Menin associates with a trithorax family histone methyltransferase complex and with the hoxc8 locus. Hughes, C.M., Rozenblatt-Rosen, O., Milne, T.A., Copeland, T.D., Levine, S.S., Lee, J.C., Hayes, D.N., Shanmugam, K.S., Bhattacharjee, A., Biondi, C.A., Kay, G.F., Hayward, N.K., Hess, J.L., Meyerson, M. Mol. Cell (2004) [Pubmed]
  24. Dynamic expression pattern of Hoxc8 during mouse early embryogenesis. Kwon, Y., Shin, J., Park, H.W., Kim, M.H. The anatomical record. Part A, Discoveries in molecular, cellular, and evolutionary biology. (2005) [Pubmed]
  25. Structural analysis of the Hox-3.1 transcription unit and the Hox-3.2--Hox-3.1 intergenic region. Awgulewitsch, A., Bieberich, C., Bogarad, L., Shashikant, C., Ruddle, F.H. Proc. Natl. Acad. Sci. U.S.A. (1990) [Pubmed]
  26. Molecules mimicking Smad1 interacting with Hox stimulate bone formation. Liu, Z., Shi, W., Ji, X., Sun, C., Jee, W.S., Wu, Y., Mao, Z., Nagy, T.R., Li, Q., Cao, X. J. Biol. Chem. (2004) [Pubmed]
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