Genome-wide binding patterns of thyroid hormone receptor beta.
Genome-wide binding patterns of thyroid hormone receptor beta.
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DOI：
10.1371/journal.pone.0081186
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发表时间：
2014
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：
Ayers S;Switnicki MP;Angajala A;Lammel J;Arumanayagam AS;Webb P
甲状腺激素（TH）受体（TRs）在代谢中起着核心作用，是药物干预的主要靶点。然而，目前关于TR结合位点全基因组定位的信息有限。因此，TR基因组分布的复杂性以及TRβ结合事件与基因调控之间的联系尚未得到充分认识。在这里，我们采用BioChIP方法在肝细胞系（HepG2）中捕获TR全基因组结合事件。像其他nr一样，TRβ在整个基因组中广泛分布。然而，转录基因的直接5′和3′结合位点显著富集，近50%的T3诱导基因可以检测到TRβ。相反，在该系统中，在负调控基因或对非配体TRs有反应的基因上没有观察到显著的TRβ富集。典型的TRβ半位点存在于90%以上的TRβ峰中，经典的TRβ半位点也非常丰富，但个体的TRE组织表现出高度的变化，半位点的取向和间距不同。在TR峰值附近，TR相关转录因子（包括AP-1和CTCF）的结合位点也显著富集。我们得出结论，T3依赖性基因诱导通常涉及近端TRβ结合事件，但一些基因的T3诱导需要远端结合事件，并且不同的间接机制通常在负调控和非配体TR作用中起作用。更好地了解TR结合位点的基因组背景将有助于我们确定TR以不同方式调节基因的原因，并确定TR作用选择性调节的可能性。
Thyroid hormone (TH) receptors (TRs) play central roles in metabolism and are major targets for pharmaceutical intervention. Presently, however, there is limited information about genome wide localizations of TR binding sites. Thus, complexities of TR genomic distribution and links between TRβ binding events and gene regulation are not fully appreciated. Here, we employ a BioChIP approach to capture TR genome-wide binding events in a liver cell line (HepG2). Like other NRs, TRβ appears widely distributed throughout the genome. Nevertheless, there is striking enrichment of TRβ binding sites immediately 5′ and 3′ of transcribed genes and TRβ can be detected near 50% of T3 induced genes. In contrast, no significant enrichment of TRβ is seen at negatively regulated genes or genes that respond to unliganded TRs in this system. Canonical TRE half-sites are present in more than 90% of TRβ peaks and classical TREs are also greatly enriched, but individual TRE organization appears highly variable with diverse half-site orientation and spacing. There is also significant enrichment of binding sites for TR associated transcription factors, including AP-1 and CTCF, near TR peaks. We conclude that T3-dependent gene induction commonly involves proximal TRβ binding events but that far-distant binding events are needed for T3 induction of some genes and that distinct, indirect, mechanisms are often at play in negative regulation and unliganded TR actions. Better understanding of genomic context of TR binding sites will help us determine why TR regulates genes in different ways and determine possibilities for selective modulation of TR action.
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影响因子：
14.9
作者：
Cui JY;Gunewardena SS;Rockwell CE;Klaassen CD
通讯作者：
Klaassen CD
DOI：
10.1073/pnas.1332608100
发表时间：
2003-06-24
影响因子：
11.1
作者：
de Boer, E;Rodriguez, P;Strouboulis, J
通讯作者：
Strouboulis, J
影响因子：
--
作者：
FORMAN, BM;CASANOVA, J;SAMUELS, HH
通讯作者：
SAMUELS, HH
全基因组分析通过过氧化物酶体增殖物激活受体-β/δ（PPARβ/δ）定义了不同的转录调节模式。
影响因子：
3.7
作者：
Adhikary T;Kaddatz K;Finkernagel F;Schönbauer A;Meissner W;Scharfe M;Jarek M;Blöcker H;Müller-Brüsselbach S;Müller R
通讯作者：
Müller R
模因套件：用于发现和搜索的工具。
影响因子：
14.9
作者：
Bailey TL;Boden M;Buske FA;Frith M;Grant CE;Clementi L;Ren J;Li WW;Noble WS
通讯作者：
Noble WS