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

被引:52
作者
Ali, Fahad R. [1 ]
Vasiliou, Sylvia A. [1 ]
Haddley, Kate [1 ]
Paredes, Ursula M. [1 ]
Roberts, Julian C. [1 ]
Miyajima, Fabio [1 ]
Klenova, Elena [2 ]
Bubb, Vivien J. [1 ]
Quinn, John P. [1 ]
机构
[1] Univ Liverpool, Sch Biomed Sci, Liverpool L69 3GE, Merseyside, England
[2] Univ Essex, Dept Biol Sci, Colchester CO4 3SQ, Essex, England
基金
英国生物技术与生命科学研究理事会; 英国惠康基金;
关键词
behaviour; CCCTC-binding factor; human serotonin transporter; polymorphism; variable number tandem repeat; MESSENGER-RNA; AFFECTIVE-DISORDERS; POLYMORPHIC REGION; ALLELIC EXPRESSION; BIPOLAR DISORDER; PROMOTER REGION; RAT-BRAIN; ASSOCIATION; 5-HTTLPR; ENHANCER;
D O I
10.1111/j.1471-4159.2009.06453.x
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:296 / 306
页数:11
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