在非洲爪蟾变态过程中，组蛋白 H3K79 甲基转移酶 Dot1L 被甲状腺激素受体直接激活。

Histone H3K79 methyltransferase Dot1L is directly activated by thyroid hormone receptor during Xenopus metamorphosis.

机构信息

Section on Molecular Morphogenesis, Program in Cellular Regulation and Metabolism (PCRM), Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institutes of Health (NIH), 18 Library Dr, Bethesda, MD, 20892, USA.

Present address: Division of Gene Structure and Function, Research Center for Genomic Medicine, Saitama Medical University, 1397-1 Yamane, Hidaka-shi, Saitama, 350-1241, Japan.

出版信息

Cell Biosci. 2012 Jul 16;2(1):25. doi: 10.1186/2045-3701-2-25.

BACKGROUND

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.

RESULTS

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.

CONCLUSIONS

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.

背景

甲状腺激素（T3）对成人器官功能和脊椎动物发育至关重要。两栖动物变态完全依赖于 T3，这为研究 T3 如何控制脊椎动物的胚胎后发育提供了一个独特的机会。早期研究表明，TR 在非洲爪蟾中介导 T3 的变态作用。配体结合的 TR 在变态过程中招募组蛋白修饰共激活因子复合物到靶基因。这导致核小体去除和组蛋白修饰，包括组蛋白 H3 赖氨酸（K）79 的甲基化，在启动子区域，并激活 T3 诱导的基因。