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

HOXD4  -  homeobox D4

Homo sapiens

Synonyms: HHO.C13, HOX-5.1, HOX4, HOX4B, Homeobox protein HHO.C13, ...
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 HOXD4


High impact information on HOXD4

  • A fusion gene consisting of a heat shock promoter attached to the human Hox-4.2 gene was introduced into the Drosophila genome, and its regulatory and developmental effects were assayed after heat shock [3].
  • The HOX3D protein, and those encoded by the downstream gene HOX3E and its paralog HOX4B are instead inactive [4].
  • The comparison to Hoxd-4 and Isl-1 indicates that this role in chondrogenesis is specific to proteins of the Hox class [5].
  • (i) Most of PBX N terminal to the homeodomain is required for efficient cooperative binding with HOXD4 and HOXD9 [6].
  • (iii) Although MEIS does not cooperatively bind DNA with ANTP class HOX proteins, it does form a trimer as a non-DNA-binding partner with DNA-bound PBX-HOXD4 [6].

Chemical compound and disease context of HOXD4

  • We have identified a 185-bp retinoid-responsive transcriptional enhancer 5' of the human HOXD4 gene, which regulates inducibility of the gene in embryonal carcinoma cells through a pattern of DNA-protein interaction on at least two distinct elements [7].

Biological context of HOXD4

  • In this study, we have used transgenic analysis of the human HOXD4 locus to identify one neural and two mesodermal 3' enhancers that are capable of mediating the proper anterior limits of expression in the hindbrain and paraxial mesoderm (somites), respectively [8].
  • The HOXD4 enhancer directs expression of a lacZ reporter gene in the neural tube of transgenic mouse embryos in a time-regulated and regionally restricted fashion, reproducing part of the anterior neuroectodermal expression pattern of the endogenous Hoxd-4 gene [7].
  • Administration of retinoic acid to developing embryos causes alterations in the spatial restriction of the transgene expression domain, indicating that the HOXD4 enhancer is also a retinoid-responsive element in vivo [7].
  • Induction of the HOXD4 promoter-enhancer in the presence of a selective RAR alpha antagonist indicated that the RAR alpha-dependent RAR beta activation is nevertheless a necessary step in HOX gene activation [9].
  • We have studied the regulation of the early activated HOXD4 gene, which is expressed in human embryogenesis in multiple transcripts generated by the developmentally controlled use of alternative transcription start sites and polyadenylation signals [9].

Anatomical context of HOXD4

  • We have analyzed the expression of homeoproteins of the HOX family in resting and activated lymphoid cells and in neoplastic lymphoid cell lines by the use of monoclonal antibodies (MoAbs) already shown to react with the homeoproteins HOXA10, HOXC6, and HOXD4, respectively [10].
  • Purified nucleoli from stimulated T lymphocytes, and Raji cells contain an activity capable of binding, in a gel retardation assay, to an oligonucleotide specifically recognised by the HOXD4 homeoprotein [11].
  • Low levels of HOXD4 and HOXD9 induction were observed in two and one RA-treated NB cell line, respectively [12].
  • In addition to directing expression in the central nervous system (CNS) up to the correct rhombomere 6/7 boundary in the hindbrain, the neural enhancer also mediates a three rhombomere anterior shift from this boundary in response to retinoic acid (RA), mimicking the endogenous Hoxd4 response [8].
  • Grafting of somites or retinoic acid-loaded beads beneath the rostral hindbrain induced the formation of somatic motoneurones in rhombomere 4 only, and Hox genes normally expressed more caudally (Hoxa3, Hoxd4) were induced in this region [13].

Associations of HOXD4 with chemical compounds

  • In vitro and transgenic analysis of a human HOXD4 retinoid-responsive enhancer [7].
  • Synthesis of NH2-VYPWMK hexapeptide confirmed this prediction; and an alanine scan of HOXD4 ablated binding by mAb 10D11 when amino acids in the putative epitope were mutated [14].
  • Using antibodies to XlHbox 1 (similar to Hox 3.3 or C6) and Hox 4.2 (or D4), we showed that there is a homeoprotein gradient within the feather buds, and that the expression pattern is position-specific [15].

Physical interactions of HOXD4


Regulatory relationships of HOXD4

  • An autoregulatory element was shown to recruit HOXD4 and its cofactor PBX1 and to positively regulate Hoxd4 expression in differentiating P19 cells [16].

Other interactions of HOXD4


Analytical, diagnostic and therapeutic context of HOXD4

  • This activity is specifically removed by anti-HOXD4 antibodies and is found associated in southwestern blots with a single band with an apparent M(r) of 30,000, corresponding to that of recombinant HOXD4 [11].


  1. Molecular mechanisms underlying the expression of the human HOX-5.1 gene. Cianetti, L., Di Cristofaro, A., Zappavigna, V., Bottero, L., Boccoli, G., Testa, U., Russo, G., Boncinelli, E., Peschle, C. Nucleic Acids Res. (1990) [Pubmed]
  2. Mutation analysis of the HOX paralogous 4-13 genes in children with acute lymphoid malignancies: identification of a novel germline mutation of HOXD4 leading to a partial loss-of-function. van Scherpenzeel Thim, V., Remacle, S., Picard, J., Cornu, G., Gofflot, F., Rezsohazy, R., Verellen-Dumoulin, C. Hum. Mutat. (2005) [Pubmed]
  3. Human Hox-4.2 and Drosophila deformed encode similar regulatory specificities in Drosophila embryos and larvae. McGinnis, N., Kuziora, M.A., McGinnis, W. Cell (1990) [Pubmed]
  4. The upstream region of the human homeobox gene HOX3D is a target for regulation by retinoic acid and HOX homeoproteins. Arcioni, L., Simeone, A., Guazzi, S., Zappavigna, V., Boncinelli, E., Mavilio, F. EMBO J. (1992) [Pubmed]
  5. Evidence for regulation of cartilage differentiation by the homeobox gene Hoxc-8. Yueh, Y.G., Gardner, D.P., Kappen, C. Proc. Natl. Acad. Sci. U.S.A. (1998) [Pubmed]
  6. PBX and MEIS as non-DNA-binding partners in trimeric complexes with HOX proteins. Shanmugam, K., Green, N.C., Rambaldi, I., Saragovi, H.U., Featherstone, M.S. Mol. Cell. Biol. (1999) [Pubmed]
  7. In vitro and transgenic analysis of a human HOXD4 retinoid-responsive enhancer. Morrison, A., Moroni, M.C., Ariza-McNaughton, L., Krumlauf, R., Mavilio, F. Development (1996) [Pubmed]
  8. HOXD4 and regulation of the group 4 paralog genes. Morrison, A., Ariza-McNaughton, L., Gould, A., Featherstone, M., Krumlauf, R. Development (1997) [Pubmed]
  9. Regulation of the human HOXD4 gene by retinoids. Moroni, M.C., Viganó, M.A., Mavilio, F. Mech. Dev. (1993) [Pubmed]
  10. Expression of HOXC4 homeoprotein in the nucleus of activated human lymphocytes. Meazza, R., Faiella, A., Corsetti, M.T., Airoldi, I., Ferrini, S., Boncinelli, E., Corte, G. Blood (1995) [Pubmed]
  11. Nucleolar localisation of three Hox homeoproteins. Corsetti, M.T., Levi, G., Lancia, F., Sanseverino, L., Ferrini, S., Boncinelli, E., Corte, G. J. Cell. Sci. (1995) [Pubmed]
  12. Up-regulation of HOXC6, HOXD1, and HOXD8 homeobox gene expression in human neuroblastoma cells following chemical induction of differentiation. Manohar, C.F., Salwen, H.R., Furtado, M.R., Cohn, S.L. Tumour Biol. (1996) [Pubmed]
  13. Somatic motoneurone specification in the hindbrain: the influence of somite-derived signals, retinoic acid and Hoxa3. Guidato, S., Prin, F., Guthrie, S. Development (2003) [Pubmed]
  14. DiSSiMiL: Diverse Small Size Mini-Libraries applied to simple and rapid epitope mapping of a monoclonal antibody. Burgess, K., Han, I., Zhang, A., Zheng, W.H., Shanmugam, K., Featherstone, M.S., Saragovi, H.U. J. Pept. Res. (2001) [Pubmed]
  15. Adhesion molecules and homeoproteins in the phenotypic determination of skin appendages. Chuong, C.M., Widelitz, R.B., Jiang, T.X. J. Invest. Dermatol. (1993) [Pubmed]
  16. Interplay between chromatin and trans-acting factors regulating the Hoxd4 promoter during neural differentiation. Kobrossy, L., Rastegar, M., Featherstone, M. J. Biol. Chem. (2006) [Pubmed]
  17. Distinct HOX N-terminal arm residues are responsible for specificity of DNA recognition by HOX monomers and HOX.PBX heterodimers. Phelan, M.L., Featherstone, M.S. J. Biol. Chem. (1997) [Pubmed]
  18. Cloning and sequencing of the human homeobox gene HOX4A. Taniguchi, Y., Fujii, A., Moriuchi, T. Biochim. Biophys. Acta (1992) [Pubmed]
WikiGenes - Universities