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首页> 外文期刊>Molecular and Cellular Biology >Thyroid Hormone Receptor α1 Directly Controls Transcription of the β-Catenin Gene in Intestinal Epithelial Cells
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Thyroid Hormone Receptor α1 Directly Controls Transcription of the β-Catenin Gene in Intestinal Epithelial Cells

机译：甲状腺激素受体α1直接控制肠道上皮细胞中β-catenin基因的转录

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Thyroid hormones, T3 and T4, are known regulators of intestine development. The best characterized example is the remodeling of the gastrointestinal tract during amphibian metamorphosis. Thyroid hormones act via nuclear receptors, the TRs, which are T3-dependent transcription factors. We previously showed that intestinal epithelial cell proliferation is controlled by thyroid hormones and the TRα gene. To analyze the mechanisms responsible, we studied the expression of genes belonging to and/or activated by the Wnt/β-catenin pathway, a major actor in the control of physiological and pathological epithelial proliferation in the intestine. We show that T3-TRα1 controls the transcription of the β-catenin gene in an epithelial cell-autonomous way. This is parallel to positive regulation of proliferation-controlling genes such as type D cyclins and c-myc, known targets of the Wnt/β-catenin. In addition, we show that the regulation of the β-catenin gene is direct, as TR binds in vitro and in chromatin in vivo to a specific thyroid hormone-responsive element present in intron 1 of this gene. This is the first report concerning in vivo transcriptional control of the β-catenin gene. As Wnt/β-catenin plays a crucial role in intestinal tumorigenesis, our observations open a new perspective on the study of TRs as potential tumor inducers.
机译：甲状腺激素T3和T4是已知的肠道发育调节剂。最有特色的例子是两栖动物变态过程中胃肠道的重塑。甲状腺激素通过核受体TRs起作用，TRs是T3依赖性转录因子。我们先前显示，肠上皮细胞增殖受甲状腺激素和TRα基因控制。为了分析负责的机制，我们研究了属于Wnt /β-catenin途径和/或由Wnt /β-catenin途径激活的基因的表达，Wnt /β-catenin途径是控制肠道生理和病理上皮细胞增殖的主要因素。我们显示，T3-TRα1以上皮细胞自主方式控制β-catenin基因的转录。这与诸如Wnt /β-catenin的已知靶标的D型细胞周期蛋白和c- myc 等增殖控制基因的阳性调控平行。此外，我们显示β-catenin基因的调节是直接的，因为TR在体外和在染色质中与该基因的内含子1中存在的特定甲状腺激素应答元件结合。这是有关β-catenin基因在体内转录控制的首次报道。由于Wnt /β-catenin在肠道肿瘤发生中起着至关重要的作用，我们的观察结果为TRs作为潜在的肿瘤诱导剂的研究开辟了新的视角。

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