Combinatorial interaction between two human serotonin transporter gene variable number tandem repeats and their regulation by CTCF.

Combinatorial interaction between two human serotonin transporter gene variable number tandem repeats and their regulation by CTCF.
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DOI:
10.1111/j.1471-4159.2009.06453.x
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发表时间:
2010-01
影响因子:
4.7
通讯作者:
Quinn JP
Quinn JP
中科院分区:
医学2区
文献类型:
--
作者:
Ali FR;Vasiliou SA;Haddley K;Paredes UM;Roberts JC;Miyajima F;Klenova E;Bubb VJ;Quinn JP

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人5-羟色胺转运蛋白基因(SLC 6A 4)内的两个不同的可变数目串联重复序列(VNTR)被认为是CNS疾病的易感因素。5′-启动子连锁多态区以22或23 bp的短(s)和长(l)等位基因存在。内含子2内的第二个(Stin 2)作为含有16或17 bp元件的9、10或12个拷贝的三个变体存在。这些VNTR,单独或组合,支持大鼠新生儿前额叶皮层文化的差异报告基因表达。来自双VNTR构建体的报告基因活性水平表明两个结构域之间的组合作用。染色质免疫沉淀表明,这两个VNTR域可以结合CCCTC结合因子,这与外源性提供的CCCTC结合因子的能力,以调节这些报告基因构建体支持的表达。我们建议,多个多态性结构域之间的相互作用的潜力,应纳入遗传关联研究。神经化学杂志。(2010)112,296-306。
Two distinct variable number tandem repeats (VNTRs) within the human serotonin transporter gene (SLC6A4) have been implicated as predisposing factors for CNS disorders. The linked polymorphic region in the 5′-promoter exists as short (s) and long (l) alleles of a 22 or 23 bp elements. The second within intron 2 (Stin2) exists as three variants containing 9, 10 or 12 copies of a 16 or 17 bp element. These VNTRs, individually or in combination, supported differential reporter gene expression in rat neonate prefrontal cortical cultures. The level of reporter gene activity from the dual VNTR constructs indicated combinatorial action between the two domains. Chromatin immunoprecipitation demonstrated that both these VNTR domains can bind the CCCTC-binding factor and this correlated with the ability of exogenously supplied CCCTC-binding factor to modulate the expression supported by these reporter gene constructs. We suggest that the potential for interaction between multiple polymorphic domains should be incorporated into genetic association studies. J. Neurochem. (2010) 112, 296–306.
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