Histone H3K79 methyltransferase Dot1L is directly activated by thyroid hormone receptor during Xenopus metamorphosis.
Histone H3K79 methyltransferase Dot1L is directly activated by thyroid hormone receptor during Xenopus metamorphosis.
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DOI：
10.1186/2045-3701-2-25
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发表时间：
2012-07-16
影响因子：
7.5
通讯作者：
Shi YB
中科院分区：
文献类型：
--
作者：
Matsuura K;Fujimoto K;Das B;Fu L;Lu CD;Shi YB
甲状腺激素（T3）对成年器官功能和脊椎动物发育很重要。两栖动物的变态完全依赖于T3，并提供了一个独特的机会，研究T3如何控制脊椎动物胚后发育。早期的研究表明，TR介导的T3在非洲爪蟾的变质作用。配体TR在变态期间招募组蛋白修饰辅激活因子复合物靶向基因。这导致核小体去除和组蛋白修饰，包括启动子区组蛋白H3赖氨酸（K）79的甲基化，以及T3诱导基因的激活。我们发现，Dot1L，唯一的组蛋白甲基转移酶能够甲基化H3K79，是直接调节TR通过结合到T3响应元件的启动子区域在非洲爪蟾热带爪蟾，一个高度相关的物种的非洲爪蟾变态。我们进一步表明，Dot1L在肠道和尾部的表达与器官的转化相关。我们的研究结果表明，TR激活Dot1L，Dot1L反过来又通过正反馈参与变态，以增强H3K79甲基化和配体TR的基因激活。
Thyroid hormone (T3) is important for adult organ function and vertebrate development. Amphibian metamorphosis is totally dependent on T3 and offers a unique opportunity to study how T3 controls postembryonic development in vertebrates. Earlier studies have demonstrated that TR mediates the metamorphic effects of T3 in Xenopus laevis. Liganded TR recruits histone modifying coactivator complexes to target genes during metamorphosis. This leads to nucleosomal removal and histone modifications, including methylation of histone H3 lysine (K) 79, in the promoter regions, and the activation of T3-inducible genes. We show that Dot1L, the only histone methyltransferase capable of methylating H3K79, is directly regulated by TR via binding to a T3 response element in the promoter region during metamorphosis in Xenopus tropicalis, a highly related species of Xenopus laevis. We further show that Dot1L expression in both the intestine and tail correlates with the transformation of the organs. Our findings suggest that TR activates Dot1L, which in turn participates in metamorphosis through a positive feedback to enhance H3K79 methylation and gene activation by liganded TR.
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