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

Ali, FR and Vasiliou, SA and Haddley, K and Paredes, UM and Roberts, JC and Miyajima, F and Klenova, E and Bubb, VJ and Quinn, JP (2010) 'Combinatorial interaction between two human serotonin transporter gene variable number tandem repeats and their regulation by CTCF.' Journal of Neurochemistry, 112 (1). 296 - 306. ISSN 0022-3042

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Abstract

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. © 2009 International Society for Neurochemistry.

Item Type: Article
Subjects: Q Science > QH Natural history > QH301 Biology
Divisions: Faculty of Science and Health > Biological Sciences, School of
Depositing User: Jim Jamieson
Date Deposited: 06 Oct 2011 09:41
Last Modified: 17 Aug 2017 18:17
URI: http://repository.essex.ac.uk/id/eprint/841

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