RNA polymerase II phosphorylation at serine 2 and histone H3 tri-methylation at,lysine 36 are key steps for thyroid hormone receptor β gene activation by thyroid hormone in Rana catesbeiana tadpole liver
RNA polymerase II phosphorylation at serine 2 and histone H3 tri-methylation at,lysine 36 are key steps for thyroid hormone receptor β gene activation by thyroid hormone in Rana catesbeiana tadpole liver
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RNA聚合酶II丝氨酸2位磷酸化和组蛋白H3赖氨酸36位三甲基化是林蛙蝌蚪肝脏中甲状腺激素激活甲状腺激素受体β基因的关键步骤
DOI：
10.1016/j.bbrc.2011.12.097
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发表时间：
2012
期刊：
影响因子：
--
通讯作者：
Yamauchi K
中科院分区：
文献类型：
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作者：
Mochizuki K;Ishihara A;Goda T;Yamauchi K
甲状腺激素（TH）是两栖动物变态所必需的激素，在变态过程中，许多基因的表达直接或间接地通过TH受体（TRs）来控制。甲状腺激素结合TR诱导辅助调节开关的TH诱导基因的调控区域：辅阻遏物与unliganded TR复合被替换的辅激活物与配体TR复合，导致转录活性状态。辅调节子的转换与组蛋白乙酰化有关。本研究采用染色质免疫沉淀（ChIP）技术，研究了3，3 ′，5-三碘甲状腺原氨酸（T3）处理和未处理的牛蛙蝌蚪肝脏中组蛋白H3和H4的乙酰化和甲基化状态。3，3 ′，5-三碘甲腺原氨酸处理3d，TRβ转录量增加19倍。这种增加与组蛋白H3中组蛋白H4和赖氨酸9的乙酰化（H3-K9）以及组蛋白H3中赖氨酸36的三甲基化（H3-K36）的增加相关。此外，RNA聚合酶II（PolII）和PolII（PolII-S2）中丝氨酸2磷酸化的量增加。这些结果表明，T3处理通过PolII-S2磷酸化增加组蛋白H3-K36三甲基化来增强PolII对肝脏中TRβ基因的延伸活性。
Thyroid hormone (TH) is essential for amphibian metamorphosis, during which the expression of many genes is controlled directly or indirectly through TH receptors (TRs). Thyroid hormone binding to TRs induces coregulator switching on regulatory regions of TH-inducible genes: corepressors complexed with unliganded TRs are replaced by coactivators complexed with liganded TR resulting in transcriptionally active states. The coregulator switching is linked to histone acetylation. In our study, we have investigated the acetylation and methylation states of histones H3 and H4 using chromatin immunoprecipitation (ChIP) assays on the 5′ coding region of the TRβ gene, a primary TH-response gene, in the liver from Rana catesbeiana tadpoles either treated with or not treated with 3,3′,5-triiodothyronine (T3). 3,3′,5-Triiodothyronine treatment for 3days increased the amount of TRβ transcript by 19-fold. This increase was associated with increases in the acetylation of histone H4 and lysine 9 in histone H3 (H3-K9), and tri-methylation of lysine 36 in histone H3 (H3-K36). In addition, the amounts of RNA polymerase II (PolII) and serine 2 phosphorylation in PolII (PolII-S2) increased. These results suggest that T3 treatment enhances the elongation activity of PolII on the TRβ gene in the liver by increasing histone H3-K36 tri-methylation through PolII-S2 phosphorylation.