An in silico investigation into the discovery of novel cis-acting elements within the intronic regions of human PAX7
School of Exercise, Biomedical and Health Science
Abstract: PAX3 and PAX7 are homologous paired box family members expressed during early neural and myogenic development. Assays of mRNA expression have proven conclusively that PAX3 and PAX7 transcripts are present in embryonal and alveolar rhabdomyosarcoma, neuroblastoma, Ewing’s sarcoma, and melanoma cell lines; the tumor-specific expression patterns correspond to expression patterns in corresponding embryonic cell lineages. The intronic regions of the PAX7 gene were analyzed using computational DNA pattern recognition methods. Several potential cis-regulatory motifs were identified in this investigation and one in particular that was common to both PAX7 and PAX3 and also to NF1, could have implications for the role of PAX7 in Alveolar Rhabdomyosarcoma and may be the cornerstone to more exciting, unique scientific investigations. Methods: In Silico biology methods are currently used in the pharmaceutical industry as an antecedent to wet chemistry and bench work. Here we employed several public online and offline programs/databases as tools to investigate the nucleotide sequences of the PAX7 gene. Results: Several potential cis-acting elements within the intronic regions of PAX7 were discovered through in silico biological methods. Transcription factors that could bind to these elements have also been identified and their association with cancer ascertained. Interestingly one cis element is found within a 155 bp sequence in intron 8 of PAX7 that surprisingly, is also found within intron 10 of PAX3 and is also found conserved within intron 23 of the NF-1 gene. Discussion: The use of In Silico Biology methods represent new, faster, cost-efficient techniques to identify novel regulatory elements that provide areas for more in depth in vitro investigations to confirm their functional effects. [Nature and Science. 2006;4(3):69-85].
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