ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2004
YB-1 and CTCF differentially regulate the 5-HTT polymorphic intron 2 enhancer which predisposes to a variety of neurological disorders.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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27 citing papers in PubMed, 81 citations in OpenAlex.
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- Serotonin transporter functional polymorphisms potentially increase risk of schizophrenia separately and as a haplotype.Scientific reports · 2022Article
- CTCF as a regulator of alternative splicing: new tricks for an old player.Nucleic acids research · 2021Review
- Genome-wide characterization of human minisatellite VNTRs: population-specific alleles and gene expression differences.Nucleic acids research · 2021Article
- Conservation, evolution, and regulation of splicing during prefrontal cortex development in humans, chimpanzees, and macaques.RNA (New York, N.Y.) · 2018Article
- Looking Beyond the 5-HTTLPR Polymorphism: Genetic and Epigenetic Layers of Regulation Affecting the Serotonin Transporter Gene Expression.Molecular neurobiology · 2017Review
- Characterization of a REST-Regulated Internal Promoter in the Schizophrenia Genome-Wide Associated Gene MIR137.Schizophrenia bulletin · 2015Article
- An evaluation of a SVA retrotransposon in the FUS promoter as a transcriptional regulator and its association to ALS.PloS one · 2014Article
- SVA retrotransposons as modulators of gene expression.Mobile genetic elements · 2014Article
- 3'poly-G-tailed ODNs inhibit F-spondin to induce cell death and neurite retraction in rat embryonic neurons.Molecular neurobiology · 2012Article
- Intronic tandem repeat in the serotonin transporter gene in Old World monkeys: a new transcriptional regulator?Journal of molecular neuroscience : MN · 2012Article
- Simultaneous genotyping of multiple polymorphisms in human serotonin transporter gene and detection of novel allelic variants.Translational psychiatry · 2011Article
- Specific sites in the C terminus of CTCF interact with the SA2 subunit of the cohesin complex and are required for cohesin-dependent insulation activity.Molecular and cellular biology · 2011Article
- Cell-specific effects of variants of the 68-base pair tandem repeat on prodynorphin gene promoter activity.Addiction biology · 2011Article
- Does CTCF mediate between nuclear organization and gene expression?BioEssays : news and reviews in molecular, cellular and developmental biology · 2010Review
- Combinatorial interaction between two human serotonin transporter gene variable number tandem repeats and their regulation by CTCF.Journal of neurochemistry · 2010Article
- A regulatory domain spanning the repeat sequence RE1 from herpes simplex virus type 1 has cell specific differential functions in trigeminal neurons and fibroblasts.FEBS letters · 2009Article
- Nuclear organization in the 3D space of the nucleus - cause or consequence?Current opinion in genetics & development · 2009Review
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Authors and funding
9 authors at 4 institutions in 3 countries.
Funding
Abstract
The serotonin transporter (5-HTT) gene contains a variable number tandem repeat (VNTR) domain within intron 2 that is often associated with a number of neurological conditions, including affective disorders. The implications of this polymorphism are not yet understood, however, we have previously demonstrated that the 5-HTT VNTR is a transcriptional regulatory domain, and the allelic variation supports differential reporter gene expression in vivo and in vitro. The aim of this study was to identify transcription factors responsible for the regulation of this VNTR. Using a yeast one-hybrid screen, we found the transcription factor Y box binding protein 1 (YB-1) interacts with the 5-HTT VNTR. Consistent with this, we demonstrate in a reporter gene assay that the polymorphic VNTR domains differentially respond to exogenous YB-1 and that YB-1 will bind to the VNTR in vitro in a sequence-specific manner. Interestingly, the transcription factor CCTC-binding factor (CTCF), previously shown to interact with YB-1, interferes with the ability of the VNTR to support YB-1-directed reporter gene expression. In addition, CTCF blocks the binding of YB-1 to its DNA recognition sequences in vitro, thus providing a possible mechanism of regulation of YB-1 activation of the VNTR by CTCF. Therefore, we have identified YB-1 and CTCF as transcription factors responsible, at least in part, for modulation of VNTR function as a transcriptional regulatory domain. Our data suggest a novel mechanism that explains, in part, the ability of the distinct VNTR copy numbers to support differential reporter gene expression based on YB-1 binding sites.
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