Microsatellite tandem repeats are abundant in human promoters and are associated with regulatory elements.
Microsatellite tandem repeats are abundant in human promoters and are associated with regulatory elements.
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DOI：
10.1371/journal.pone.0054710
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Gemmell N
中科院分区：
文献类型：
--
作者：
Sawaya S;Bagshaw A;Buschiazzo E;Kumar P;Chowdhury S;Black MA;Gemmell N
串联重复序列是一种易于改变重复序列数量的基因组元件，因此常常是多态的。这些序列在人类基因的启动子中以高密度的形式被发现。越来越多的经验证据表明，这些串联重复序列中的长度变化可以影响基因调控。有一类串联重复序列，称为微卫星，重复次数迅速变化。已知一些由微卫星引起的遗传变异会导致表型变异。最近，我们的团队开发了一种新的方法来衡量微卫星的进化保守性，并由此发现，转录起始点附近的人类微卫星通常是高度保守的。在这项研究中，我们研究了启动子中发现的微卫星的性质。我们在基因的起始处发现了高密度的微卫星。我们使用小波分析证明了微卫星与启动子的统计关联，这使得我们能够在多个尺度上测试关联并控制其他启动子相关元件。由于启动子微卫星往往富含G/C，我们推测富含G/C的调控元件可能驱动微卫星与启动子之间的关联。我们的结果表明，CpG岛、G-四链(G4)和未翻译的调节区与微卫星有非常显著的关联，但在分析中控制这些元件并不能消除微卫星和启动子之间的关联。由于它们的内在不稳定性以及它们与预测的功能元件的重叠，这些结果表明许多启动子微卫星有可能通过产生调控元件的突变来影响人类的表型，最终可能导致疾病。在此背景下，我们讨论了人类启动子微卫星的潜在功能。
Tandem repeats are genomic elements that are prone to changes in repeat number and are thus often polymorphic. These sequences are found at a high density at the start of human genes, in the gene’s promoter. Increasing empirical evidence suggests that length variation in these tandem repeats can affect gene regulation. One class of tandem repeats, known as microsatellites, rapidly alter in repeat number. Some of the genetic variation induced by microsatellites is known to result in phenotypic variation. Recently, our group developed a novel method for measuring the evolutionary conservation of microsatellites, and with it we discovered that human microsatellites near transcription start sites are often highly conserved. In this study, we examined the properties of microsatellites found in promoters. We found a high density of microsatellites at the start of genes. We showed that microsatellites are statistically associated with promoters using a wavelet analysis, which allowed us to test for associations on multiple scales and to control for other promoter related elements. Because promoter microsatellites tend to be G/C rich, we hypothesized that G/C rich regulatory elements may drive the association between microsatellites and promoters. Our results indicate that CpG islands, G-quadruplexes (G4) and untranslated regulatory regions have highly significant associations with microsatellites, but controlling for these elements in the analysis does not remove the association between microsatellites and promoters. Due to their intrinsic lability and their overlap with predicted functional elements, these results suggest that many promoter microsatellites have the potential to affect human phenotypes by generating mutations in regulatory elements, which may ultimately result in disease. We discuss the potential functions of human promoter microsatellites in this context.
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影响因子：
14.9
作者：
Baral A;Kumar P;Halder R;Mani P;Yadav VK;Singh A;Das SK;Chowdhury S
通讯作者：
Chowdhury S
影响因子：
3.3
作者：
Buschiazzo, Emmanuel;Gemmell, Neil J.
通讯作者：
Gemmell, Neil J.
DOI：
10.1089/oli.1.1997.7.125
发表时间：
1997-04-01
期刊：
ANTISENSE & NUCLEIC ACID DRUG DEVELOPMENT
影响因子：
--
作者：
Beaulieu, M;Barbeau, B;Rassart, E
通讯作者：
Rassart, E
影响因子：
3.9
作者：
Borel, Christelle;Migliavacca, Eugenia;Antonarakis, Stylianos E.
通讯作者：
Antonarakis, Stylianos E.
影响因子：
7.1
作者：
Allayee, Hooman;Baylin, Ana;Campos, Hannia
通讯作者：
Campos, Hannia