porcine FIT1 gene regulation

  • 文章类型: Journal Article
    脂肪诱导的转录物1(FIT1/FITM1)基因是保守基因家族的成员,对富含甘油三酸酯的脂滴积累很重要。FIT1基因在猪中表现出相似的肌肉特异性表达,老鼠,和人类。因此,猪可以作为由FIT1基因的错误表达导致的许多人类疾病的有用模型。骨骼肌中的甘油三酯含量对猪肉的品质和风味起着关键作用。猪FIT1编码区的插入/缺失突变显示出与一系列脂肪性状的高度相关性。为了更好地了解FIT1基因在人类疾病中的潜在作用以及与猪肉品质的相关性,我们的注意力集中在猪FIT1编码序列的上游区域.我们克隆了猪FIT1基因5'侧翼区的〜1kb,以确定该序列在调节生肌表达中的作用。鉴定了在肌肉发生期间激活猪FIT1启动子活性的典型E-box元件。进一步的分析表明,启动子活性是由MyoD1的过表达诱导的,MyoD1在C2C12分化过程中与该典型的E-box结合。这是FIT1作为MyoD的直接新靶标参与肌肉发育的第一个证据。
    Fat-induced transcript 1 (FIT1/FITM1) gene is a member of the conserved gene family important for triglyceride-rich lipid droplet accumulation. FIT1 gene displays a similar muscle-specific expression across pigs, mice, and humans. Thus pigs can act as a useful model of many human diseases resulting from misexpression of FIT1 gene. Triglyceride content in skeletal muscle plays a key role in pork meat quality and flavors. An insertion/deletion mutation in porcine FIT1 coding region shows a high correlation with a series of fat traits. To gain better knowledge of the potential role of FIT1 gene in human diseases and the correlations with pork meat quality, our attention is given to the region upstream of the porcine FIT1 coding sequence. We cloned ~1 kb of the 5\'-flanking region of porcine FIT1 gene to define the role of this sequence in modulating the myogenic expression. A canonical E-box element that activated porcine FIT1 promoter activity during myogenesis was identified. Further analysis demonstrated that promoter activity was induced by overexpression of MyoD1, which bound to this canonical E-box during C2C12 differentiation. This is the first evidence that FIT1 as the direct novel target of MyoD is involved in muscle development.
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