Regulatory effect of NK homeobox 1 (NKX2.1) on melanocortin 4 receptor (Mc4r) promoter in Mandarin fish
Regulatory effect of NK homeobox 1 (NKX2.1) on melanocortin 4 receptor (Mc4r) promoter in Mandarin fish
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DOI：
10.1002/jcp.31139
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发表时间：
2023-10-18
影响因子：
5.6
通讯作者：
Jia，Xiao-Dan
中科院分区：
文献类型：
--
作者：
Xu，Di-Mei;He，Shan;Jia，Xiao-Dan
黑皮质素4受体（MC4R）是一种G蛋白偶联转运蛋白，介导甲状腺激素和瘦素对能量平衡和食物摄入的调节。然而，甲状腺激素和瘦素对鱼类Mc4r基因转录调控的机制却鲜有报道。Mc4r基因mRNA在脑组织中的表达量显著高于其它组织。我们对Mc4r启动子的一段2029 bp的序列进行了结构和功能分析。同时，过表达NKX2.1和与瘦素孵育显著增加Mc4r启动子活性，但三碘甲腺原氨酸表现出相反的效果。此外，NKX2.1结合位点的突变不仅消除了瘦素对Mc4r启动子活性的激活，而且消除了甲状腺激素对Mc4r启动子活性的抑制作用。综上所述，甲状腺激素和瘦素可能通过NKX2.1调控Mc4r的转录表达。
The melanocortin 4 receptor (MC4R) is a G protein‐coupled transporter that mediates the regulation of thyroid hormones and leptin on energy balance and food intake. However, the mechanisms of transcriptional regulation ofMc4rby thyroid hormone and leptin in fish have been rarely reported. The messenger RNA expression ofMc4rgene was significantly higher in brain than those in other tissues of mandarin fish. We analyzed the structure and function of a 2029 bp sequence ofMc4rpromoter. Meanwhile, overexpression of NKX2.1 and incubation with leptin significantly increasedMc4rpromoter activity, but triiodothyronine showed the opposite effect. In addition, mutations in the NKX2.1 binding site abolished not only the activation ofMc4rpromoter activity by leptin but also the inhibitory effect of thyroid hormones onMc4rpromoter activity. In summary, these results suggested that thyroid hormones and leptin might regulate the transcriptional expression ofMc4rthrough NKX2.1.