Thyroid hormone (T3) plays an important role in vertebrate development. Compared to the postembryonic development of uterus-enclosed mammalian embryos, T3-dependent amphibian metamorphosis is advantageous for studying the function of T3 and T3 receptors (TRs) during vertebrate development. The effects of T3 on the metamorphosis of anurans such as Xenopus tropicalis is known to be mediated by TRs. Many putative TR target genes have been identified previously. Among them is the tRNA methyltransferase Mettl1. We studied the regulation of Mettl1 gene by T3 during intestinal metamorphosis, a process involves near complete degeneration of the larval epithelial cells via apoptosis and de novo formation of adult epithelial stem cells and their subsequent proliferation and differentiation. We observed that Mettl1 was activated by T3 in the intestine during both natural and T3-induced metamorphosis and that its mRNA level peaks at the climax of intestinal remodeling. We further showed that Mettl1 promoter could be activated by liganded TR via a T3 response element upstream of the transcription start site in vivo. More importantly, we found that TR binding to the TRE region correlated with the increase in the level of H3K79 methylation, a transcription activation histone mark, and the recruitment of RNA polymerase II by T3 during metamorphosis. Our findings suggest that Mettl1 is activated by liganded TR directly at the transcriptional level via the TRE in the promoter region in the intestine during metamorphosis. Mettl1 in turn regulate target tRNAs to affect translation, thus facilitating stem cell formation and/or proliferation during intestinal remodeling.

中文翻译：

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甲状腺激素受体直接激活 tRNA 甲基转移酶样 1 (Mettl1) 基因暗示热带非洲爪蟾变态过程中成体肠道干细胞发育和增殖的作用。

甲状腺激素 (T3) 在脊椎动物发育中起重要作用。与子宫封闭哺乳动物胚胎的胚后发育相比，依赖T3的两栖动物变态有利于研究脊椎动物发育过程中T3和T3受体（TRs）的功能。已知 T3 对热带爪蟾等无尾动物变态的影响是由 TRs 介导的。许多推定的TR靶基因先前已被鉴定。其中包括 tRNA 甲基转移酶 Mettl1。我们研究了肠道变态过程中 T3 对 Mettl1 基因的调节，这一过程涉及通过凋亡和成体上皮干细胞从头形成及其随后的增殖和分化使幼虫上皮细胞几乎完全退化。我们观察到 Mettl1 在自然和 T3 诱导的变态过程中被肠道中的 T3 激活，并且其 mRNA 水平在肠道重塑的高潮时达到峰值。我们进一步表明，Mettl1 启动子可以通过体内转录起始位点上游的 T3 反应元件被配体 TR 激活。更重要的是，我们发现 TR 与 TRE 区域的结合与 H3K79 甲基化水平的增加、转录激活组蛋白标记以及 T3 在变态过程中募集 RNA 聚合酶 II 相关。我们的研究结果表明，Mettl1 在变态过程中通过肠道启动子区域中的 TRE 在转录水平直接被配体 TR 激活。Mettl1 反过来调节目标 tRNA 以影响翻译，