Gene specific actions of thyroid hormone receptor subtypes.
Gene specific actions of thyroid hormone receptor subtypes.
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DOI：
10.1371/journal.pone.0052407
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Webb P
中科院分区：
文献类型：
--
作者：
Lin JZ;Sieglaff DH;Yuan C;Su J;Arumanayagam AS;Firouzbakht S;Cantu Pompa JJ;Reynolds FD;Zhou X;Cvoro A;Webb P
甲状腺激素（TH）受体有两个同源的受体（TR α和TR β），它们是核激素受体（NR）家族的成员。虽然TR在体内调节不同的过程，其他高度相关的NR调节不同的基因组，TR作用的初步研究显示，在单个基因水平上，它们的作用几乎完全重叠。在这里，我们通过比较两种细胞背景（HepG 2和HeLa）中稳定表达的相同水平的外源TR +/− T3的影响，评估了TRα和TRβ在靶基因调控方面的差异程度。我们发现，数百个基因响应T3或unliganded TR在这两种细胞类型，但无法检测到完全TR亚型特异性基因调控的可验证的例子。然而，TR的作用远非相同，我们在HepG 2细胞中检测到TR亚型特异性对整体T3反应动力学的影响，并在单个基因水平上检测到TR亚型特异性的许多例子，包括对TR +/− T3反应幅度的影响，TR调节模式和T3剂量反应。环己酰亚胺（CHX）治疗证实，至少有一些差异效应涉及可验证的直接TR靶基因。TR亚型/基因特异性效应出现在靶基因反应的广泛变化的背景下，我们认为，TR作用机制的基因选择性效应突出了在特定基因环境中出现的TR亚型功能的差异。我们建议，差异TR行动可能会影响生理和药理学反应TH和选择性TR调节剂（STRM）。
There are two homologous thyroid hormone (TH) receptors (TRs α and β), which are members of the nuclear hormone receptor (NR) family. While TRs regulate different processes in vivo and other highly related NRs regulate distinct gene sets, initial studies of TR action revealed near complete overlaps in their actions at the level of individual genes. Here, we assessed the extent that TRα and TRβ differ in target gene regulation by comparing effects of equal levels of stably expressed exogenous TRs +/− T3 in two cell backgrounds (HepG2 and HeLa). We find that hundreds of genes respond to T3 or to unliganded TRs in both cell types, but were not able to detect verifiable examples of completely TR subtype-specific gene regulation. TR actions are, however, far from identical and we detect TR subtype-specific effects on global T3 response kinetics in HepG2 cells and many examples of TR subtype specificity at the level of individual genes, including effects on magnitude of response to TR +/− T3, TR regulation patterns and T3 dose response. Cycloheximide (CHX) treatment confirms that at least some differential effects involve verifiable direct TR target genes. TR subtype/gene-specific effects emerge in the context of widespread variation in target gene response and we suggest that gene-selective effects on mechanism of TR action highlight differences in TR subtype function that emerge in the environment of specific genes. We propose that differential TR actions could influence physiologic and pharmacologic responses to THs and selective TR modulators (STRMs).
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影响因子：
158.5
作者：
Bochukova, Elena;Schoenmakers, Nadia;Chatterjee, Krishna
通讯作者：
Chatterjee, Krishna
DOI：
10.1073/pnas.0911024106
发表时间：
2009-12-08
影响因子：
11.1
作者：
Martinez, Leandro;Nascimento, Alessandro S.;Polikarpov, Igor
通讯作者：
Polikarpov, Igor
DOI：
10.1111/j.2517-6161.1995.tb02031.x
发表时间：
1995-01-01
影响因子：
5.8
作者：
BENJAMINI, Y;HOCHBERG, Y
通讯作者：
HOCHBERG, Y
影响因子：
--
作者：
Feng, X;Jiang, Y;Yen, PM
通讯作者：
Yen, PM
影响因子：
8.2
作者：
Weiss, R E;Refetoff, S
通讯作者：
Refetoff, S