Skip to main content


Buy Article:

$51.00 plus tax (Refund Policy)



We demonstrated that the genotype of the variable number tandem repeats (VNTRs) in the linked polymorphic region (LPR) of the 5′ promoter and in the intron 2 (Stin2) transcriptional regulatory domains of the serotonin transporter SLC6A4 gene determined its promoter interactions with transcription factors and co‐activators in response to cocaine in the JAr cell line. The LPR variants contain 14 (short, s) or 16 (long, l) copies of a 22–23 bp repeat element, whereas the Stin2 VNTR exists as three variants containing 9, 10 or 12 copies of a 16–17 bp repeat. We observed a differential effect of cocaine on the association of the promoter with the transcription factor CTCF, which bound to both LPR alleles prior to cocaine exposure but only to the l‐allele following exposure. Significantly, this differential effect of cocaine was correlated with the binding of the transcriptional regulator MeCP2 specifically to the s‐allele and recruiting the histone deacetylase complex (HDAC). Concurrently, cocaine increased the association of positive histone marks over the SLC6A4 gene locus. At the Stin2 domain, we lost binding of the transcription factor YB‐1, while CTCF remained bound. Our biochemical data are consistent with differential reporter gene activity directed by the individual or dual domains in response to cocaine in an Epstein–Barr virus‐based episome model of stable transfections. These observations suggest that exposure of JAr cells to cocaine may result in differential binding of transcription factors and activators based on a specific genotype that might alter epigenetic parameters affecting gene expression after the initial challenge.

Document Type: Research Article


Affiliations: 1: Institute of Translational Medicine, University of Liverpool, UK and 2: Department of Biology, Technische Universit├Ąt Darmstadt, Germany

Publication date: January 1, 2012

Access Key

Free Content
Free content
New Content
New content
Open Access Content
Open access content
Partial Open Access Content
Partial Open access content
Subscribed Content
Subscribed content
Free Trial Content
Free trial content
Cookie Policy
Cookie Policy
Ingenta Connect website makes use of cookies so as to keep track of data that you have filled in. I am Happy with this Find out more