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首页> 外文期刊>Genomics >Identification of target genes regulated by PAX3 and PAX3-FKHR in embryogenesis and alveolar rhabdomyosarcoma.
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Identification of target genes regulated by PAX3 and PAX3-FKHR in embryogenesis and alveolar rhabdomyosarcoma.

机译：鉴定在胚胎发生和肺泡横纹肌肉瘤中受PAX3和PAX3-FKHR调节的靶基因。

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PAX3 is a transcription factor important for neural, muscle, and facial development in vertebrates. To identify genes regulated by PAX3, we used a cyclic amplification and selection of targets (CASTing) strategy to isolate cis-regulatory elements bound by PAX3. CASTing libraries were constructed with mouse DNA fragments bound by mouse PAX3, and human genomic DNA fragments bound by human PAX3 and the fusion protein PAX3-FKHR. Approximately 1000 clones were sequenced from each of these three libraries. Numerous putative targets of PAX3 and PAX3-FKHR were identified and six genes, Itm2A, Fath, FLT1, TGFA, BVES, and EN2, were examined closely. The genomic DNA fragments near these genes contain PAX3 binding sites and confer PAX3-dependent regulation. The expression levels of these genes correlate with the PAX3 expression levels in mouse embryos or with PAX3-FKHR expression levels in rhabdomyosarcoma cell lines, and indicate they may be part of the PAX3 regulatory circuitry during embryogenesis and tumor formation.
机译：PAX3是对脊椎动物神经，肌肉和面部发育重要的转录因子。为了鉴定受PAX3调控的基因，我们使用了循环扩增和靶标选择（CASTing）策略来分离受PAX3约束的顺式调控元件。用与小鼠PAX3结合的小鼠DNA片段，与人PAX3和融合蛋白PAX3-FKHR结合的人基因组DNA片段构建CASTing文库。从这三个文库的每一个中测序出大约1000个克隆。确定了PAX3和PAX3-FKHR的许多推定靶标，并密切检查了Itm2A，Fath，FLT1，TGFA，BVES和EN2这六个基因。这些基因附近的基因组DNA片段包含PAX3结合位点，并赋予PAX3依赖性调控。这些基因的表达水平与小鼠胚胎中的PAX3表达水平或横纹肌肉瘤细胞系中的PAX3-FKHR表达水平相关，表明它们可能是胚胎发生和肿瘤形成过程中PAX3调控电路的一部分。

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