Disease relevance of HOXD9

• Activation of HOXD9 was observed in cultured synoviocytes infected with HTLV-I in vitro as well as in those transfected with HTLV-I tax [1].
• Western blotting and immunohistochemical analysis showed that the HOXD9 protein was expressed in the synovium from patients with RA, but not in those from patients with osteoarthritis or healthy individuals [2].

High impact information on HOXD9

• Complete or partial HOXD8/HOXD9 homeo domain swapping indicates that the ability to recognize, and activate transcription from, the HCR target in vivo depends on the amino terminus and helix 1 of the homeo domain [3].
• Functional interaction between HMG1 and HOXD9 is dependent on the DNA binding activity of the homeodomain, and requires the HOXD9 transcriptional activation domain [4].
• HOX4C and HOX4D proteins synthesized in bacteria bind to the same conserved sequence located around position -120, as well as to the TATA box and immediately upstream and downstream nucleotides [5].
• Using cotransfection experiments, we show that this endogenous DNA sequence can mediate transactivation by the HOX4D and HOX4C proteins and that this effect requires the presence of TAAT-related binding sites [6].
• A 117-kb microdeletion removing HOXD9-HOXD13 and EVX2 causes synpolydactyly [7].

Biological context of HOXD9

• HMG1 enhances, in a dose-dependent fashion, the sequence-specific DNA binding activity in vitro, and the transcriptional activation in a co-transfection assay in vivo, of the HOXD9 protein [4].
• HOXD9 transfection induced stable HOXD9 protein expression in synoviocytes and showed an increased proliferation rate under both normal and serum-starved conditions, as well as an enhanced capacity to proliferate anchorage independently to form colonies in soft agar cultures, compared with control transfectants [8].
• In addition, they suggest that the involvement of HOXD9 in the regulation of cellular growth might be mediated, at least in part, by up-regulation of growth-related factors such as bFGF and c-Fos and/or might result from increased transcription activity by its regulators [8].
• In addition, nucleotide sequence analysis of the homeobox regions of cloned Hox-4.3 and Hox-4.2 genomic DNA revealed some differences in nucleotide sequences and in the deduced homeodomain amino acid sequences compared with the sequences that have been reported [9].
• Finally, HOX4 includes 6 homeoboxes in 70 kb on chromosome 2 [10].

Anatomical context of HOXD9

• RESULTS: Expression of HOXD9 was detected in embryonic joints, preferentially on articular cartilage, only during the early stages of joint development (up to E15), whereas other HOXD genes were expressed throughout the embryonic and neonatal stages [1].
• The HOXD9-positive cells were localized in both the lining and sublining areas of the synovium [2].
• Transient cotransfection assays of NIH3T3 fibroblasts and synoviocytes showed that HOXD9 activated the luciferase reporter construct containing the highly conserved region (HCR), an autoregulatory element of HOXD9 promoter [8].
• Our data indicate that HOXD9 and ATBF1 are expressed in cervical cancer, but not in normal cervix [11].
• RESULTS: Using an in situ RT assay, specific expression of HOX4C mRNA was detected in 3 of 4 RA synovial samples, whereas none of the OA synovia expressed HOX4C [12].

Associations of HOXD9 with chemical compounds

• The binding activity of a transcriptional regulator of the HOX4C gene, C2, was analyzed by the mobility shift assay [12].

Other interactions of HOXD9

• These results show that the HOX4D and HOX4C genes are genuine sequence-specific transcription factors and suggest that, as in Drosophila, cross-regulatory interactions between these genes might be essential for their proper expression [6].
• Expression of murine HOXD9 during embryonic joint patterning and in human T lymphotropic virus type I tax transgenic mice with arthropathy resembling rheumatoid arthritis [1].
• By sequencing directly across the deletion breakpoint, we show that this microdeletion removes only HOXD9-HOXD13 and EVX2 [7].
• (i) Most of PBX N terminal to the homeodomain is required for efficient cooperative binding with HOXD4 and HOXD9 [13].
• Transcriptional regulation of the HOX4C gene by basic fibroblast growth factor on rheumatoid synovial fibroblasts [12].

Analytical, diagnostic and therapeutic context of HOXD9

• Sequence analysis of the homeobox-containing exon of the murine Hox-4.3 homeogene [14].
• RT-PCR expression analysis further showed that HOXD9 and ATBF1 were differentially expressed in cancer cells and not in normal cervix [11].
• The presence of HOX4C mRNA was also confirmed by RT-PCR and Southern blotting [12].

References