Alternative titles; symbols
HGNC Approved Gene Symbol: HOXC8
Cytogenetic location: 12q13.13 Genomic coordinates (GRCh38) : 12:54,008,985-54,012,769 (from NCBI)
Simeone et al. (1988) identified the HOXC8 gene within the HOX3 cluster on chromosome 12q13. They concluded that 3 homeobox sequences on chromosome 12 represent a single transcription unit. Primary transcripts are alternatively processed to give mature messages with a common 5-prime noncoding exon encoding different proteins containing 1 of the 3 homeodomains. See also HOXC9 (142971).
Yueh et al. (1998) showed that overexpression of a Hoxc8 transgene causes cartilage defects whose severity depends on transgene dosage. The abnormal cartilage is characterized by an accumulation of proliferating chondrocytes and reduced maturation. Since Hoxc8 is normally expressed in chondrocytes, these results suggested that Hoxc8 continues to regulate skeletal development well beyond pattern formation in a tissue-specific manner, presumably by controlling the progression of cells along the chondrocyte differentiation pathway. They found that Hoxd4 (142981) and Hoxc8 appear to act on chondrocyte differentiation in a similar manner. The protein sequences of the 2 share 67% identity within the homeodomain and 50% in the hexapeptide motif but little similarity in the remaining 70% of the molecules. Isl1, which shares no significant sequence similarities with Hoxc8 or Hoxd4, is not associated with abnormalities of skeletal development, implying that the cartilage abnormalities are specifically induced by HOX genes. The capacity of the HOX genes to regulate cartilage differentiation suggests that they may be involved in human chondrodysplasias or other cartilage disorders.
Yekta et al. (2004) found that miR196 (608632), an miRNA encoded at 3 paralogous locations in the A, B, and C mammalian HOX clusters, has extensive evolutionarily conserved complementarity to messages of HOXB8 (142963), HOXC8, and HOXD8 (142985). Cell culture experiments demonstrated downregulation of HOXB8, HOXC8, HOXD8, and HOXA7 (142950) and supported the cleavage mechanism for miR196-directed repression of HOXB8.
By in situ hybridization and somatic cell genetic techniques, Rabin et al. (1986) mapped the human cognate of the murine Hox-3 locus to chromosome 12q11-q21. The murine locus is on chromosome 15 (Schughart et al., 1989). Cannizzaro et al. (1987) mapped HOX3 to chromosome 12q12-q13 by Southern blot analysis of somatic cell hybrids and by in situ hybridization.
As reviewed by Acampora et al. (1989), the homeobox region 3, which maps to chromosome 12q12-q13, contains at least 7 homeobox genes in 160 kb of DNA. HOX3A is homologous to mouse Hox-3.1; HOX3B (142971) to mouse Hox-3.2; HOX3C (142972) to mouse Hox-6.1, and HOX3D (142973) to mouse Hox-6.2. The order of genes, from 5-prime to 3-prime, is HOX3G (142976), HOX3F (142975), HOX3B, HOX3A, HOX3C (142972), HOX3D, HOX3E (142974) (Acampora et al., 1989). Masuda et al. (1991) mapped the feline equivalent to chromosome B4, which shares syntenic homology with human chromosome 12 and mouse chromosome 15.
Acampora, D., D'Esposito, M., Faiella, A., Pannese, M., Migliaccio, E., Morelli, F., Stornaiuolo, A., Nigro, V., Simeone, A., Boncinelli, E. The human HOX gene family. Nucleic Acids Res. 17: 10385-10402, 1989. [PubMed: 2574852] [Full Text: https://doi.org/10.1093/nar/17.24.10385]
Cannizzaro, L. A., Croce, C. M., Griffin, C. A., Simeone, A., Boncinelli, E., Huebner, K. Human homeo box-containing genes located at chromosome regions 2q31-2q37 and 12q12-12q13. Am. J. Hum. Genet. 41: 1-15, 1987. [PubMed: 2886047]
Masuda, R., Yuhki, N., O'Brien, S. J. Molecular cloning, chromosomal assignment, and nucleotide sequence of the feline homeobox HOX3A. Genomics 11: 1007-1013, 1991. [PubMed: 1686012] [Full Text: https://doi.org/10.1016/0888-7543(91)90026-b]
Rabin, M., Ferguson-Smith, A., Hart, C. P., Ruddle, F. H. Cognate homeo-box loci mapped on homologous human and mouse chromosomes. Proc. Nat. Acad. Sci. 83: 9104-9108, 1986. [PubMed: 2878432] [Full Text: https://doi.org/10.1073/pnas.83.23.9104]
Schughart, K., Pravtcheva, D., Newman, M. S., Hunihan, L. W., Jiang, Z., Ruddle, F. H. Isolation and regional localization of the murine homeobox-containing gene Hox-3.3 to mouse chromosome region 15E. Genomics 5: 76-83, 1989. [PubMed: 2570032] [Full Text: https://doi.org/10.1016/0888-7543(89)90089-x]
Simeone, A., Pannese, M., Acampora, D., D'Esposito, M., Boncinelli, E. At least three human homeoboxes on chromosome 12 belong to the same transcription unit. Nucleic Acids Res. 16: 5379-5390, 1988. [PubMed: 2898768] [Full Text: https://doi.org/10.1093/nar/16.12.5379]
Yekta, S., Shih, I., Bartel, D. P. MicroRNA-directed cleavage of HOXB8 mRNA. Science 304: 594-596, 2004. [PubMed: 15105502] [Full Text: https://doi.org/10.1126/science.1097434]
Yueh, Y. G., Gardner, D. P., Kappen, C. Evidence for regulation of cartilage differentiation by the homeobox gene Hoxc-8. Proc. Nat. Acad. Sci. 95: 9956-9961, 1998. [PubMed: 9707582] [Full Text: https://doi.org/10.1073/pnas.95.17.9956]