Disease relevance of HOXB3

• DNase I footprinting experiments show that the two sites bind HOXB3 protein synthesized in both Escherichia coli and eukaryotic cells, as well as nuclear factor(s) present in protein extracts obtained from mouse embryonic tissues which express group 3 Hox genes and TTF-1 [1].
• The glioblastoma cell line, 251-MG expresses almost all of the genes of the HOX2 locus [2].
• The two uninduced neuroblastoma cell lines show a similar pattern of expression for a number of HOX2 genes although the levels of expression are different for individual cell lines [2].
• Immunocytochemical detection of the homeobox B3, B4, and C6 gene products in breast carcinomas [3].
• The embryonal carcinoma cell line F9 expresses low levels of several HOX2 genes which is restricted to the 5' region of the HOX2 cluster [2].

High impact information on HOXB3

• To gain some insight into the role this gene may play in hematopoiesis, HOXB3 was overexpressed in murine bone marrow cells using retroviral gene transfer [4].
• Homeobox B3 promotes capillary morphogenesis and angiogenesis [5].
• Transactivation by HOXB3 is mediated by two binding sites containing an ATTA core located at -100 and +30 from the transcription start site [1].
• HOXB3 is expressed in early mammalian embryogenesis in the anterior neuroectoderm, branchial arches and their derivatives, including the area of the thyroid primordia and thyroid gland [1].
• A 862 bp 5' genomic fragment of the rat TTF-1 gene, conferring thyroid-specific expression to a reporter gene, was sufficient to mediate transactivation by the human HOXB3 gene in co-transfection assay in both NIH3T3 or HeLa cells [1].

Biological context of HOXB3

• HOX2 includes 9 homeoboxes in 180 kb on chromosome 17 [6].
• HOXB1, HOXB3, and nuclear extracts from 12.5 days postcoitum mouse embryos bind to a sequence containing two palindromic TAATTA sites, which bear four copies of the ATTA core sequence, a common feature of most HOM-C/HOX binding sites [7].
• The region bound by the three homeoproteins is strikingly conserved through evolution and necessary (at least for HOXB1 and HOXB3) to mediate the up-regulation of the Otx2 transcription [7].
• A comparison of the predicted HOX4A protein with the HOX2G protein revealed four regions of amino acid sequence similarities: an N-terminal tetrapeptide, a pentapeptide (pre-box) upstream of the homeodomain, the homeodomain and a C-terminal octapeptide [8].
• The finished sequence from BAC clones from the genome of the sea urchin, Strongylocentrotus purpuratus, reveals a gene order wherein the anterior genes (Hox1, Hox2 and Hox3) lie nearest the posterior genes in the cluster such that the most 3' gene is Hox5 [9].

Anatomical context of HOXB3

• In addition, expression of certain genes, including HOXB3 and HOXB4, is largely restricted to the long-term culture-initiating cell enriched pool, containing the putative stem cell population [10].
• HOXB3 mRNA levels are high in the earliest CD34+ lineage- bone marrow cells and low to undetectable in later CD34+/CD34- cells [4].
• Differential expression of human HOX-2 genes along the anterior-posterior axis in embryonic central nervous system [11].
• Homeobox B3, FoxA1 and FoxA2 interactions in epithelial lung cell differentiation of the multipotent M3E3/C3 cell line [12].
• In conclusion, our analysis reveals a complex pattern of expression for the genes of the HOX2 locus in neuronal and glial cells and suggests that the cell-specific expression of these genes may be correlated with the phenotypic differences that are observed between different neuronal and glial cell populations within the nervous system [2].

Associations of HOXB3 with chemical compounds

• Recently, it has been shown that expression of human HOX 2 genes is sequentially activated by RA beginning from Hox 2.9 at the 3' end of the HOX 2 cluster (A. Simeone, D. Acampora, L. Arcioni, P. W. Andrews, E. Boncinelli, and F. Mavilio, Nature [London] 346:763-766, 1990) [13].
• Immunocytochemical detection of the homeobox B3, B4, and C6 gene products within the human thymic cellular microenvironment [14].

Other interactions of HOXB3

• FLT3 mRNA levels were correlated with the expression of multiple HOX genes, whereas FLT3 mutations were correlated with HOXB3 [15].
• A novel intronic polymorphism (intron 2 +130 (CT)n) in the human homeobox gene HOXB3 [16].
• However, the HOX2G protein, which exhibits a paralogous relationship with the HOX4A protein, does not possess the sequence which is similar to that in pp60c-src [8].

Analytical, diagnostic and therapeutic context of HOXB3

• Thymi of HOXB3 marrow recipients were reduced in size compared with control transplant recipients, with a 24-fold decrease in the absolute number of CD4+ CD8+ cells and a 3-fold increase in the number of CD4- CD8- thymocytes that contained a high proportion of gammadelta TCR+ cells [4].
• We have also investigated the region-specific expression of HOX-2 genes in human embryonic-fetal life by Northern-blot analysis [11].
• Homeobox B3, B4, and C6 gene product expression in osteosarcomas as detected by immunocytochemistry [17].

References