Open Access Research article

Characterisation of the potential function of SVA retrotransposons to modulate gene expression patterns

Abigail L Savage1, Vivien J Bubb1, Gerome Breen23 and John P Quinn1*

Author Affiliations

1 Department of Molecular and Clinical Pharmacology, Institute of Translational Medicine, The University of Liverpool, Liverpool L69 3BX, UK

2 King’s College London, MRC Social Genetic and Developmental Psychiatry Research Centre, Institute of Psychiatry, London, UK

3 National Institute for Health Research (NIHR) Biomedical Research Centre for Mental Health, South London and Maudsley NHS Foundation Trust and Institute of Psychiatry, King’s College London SE5 8DF, UK

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BMC Evolutionary Biology 2013, 13:101  doi:10.1186/1471-2148-13-101

Published: 21 May 2013

Abstract

Background

Retrotransposons are a major component of the human genome constituting as much as 45%. The hominid specific SINE-VNTR-Alus are the youngest of these elements constituting 0.13% of the genome; they are therefore a practical and amenable group for analysis of both their global integration, polymorphic variation and their potential contribution to modulation of genome regulation.

Results

Consistent with insertion into active chromatin we have determined that SVAs are more prevalent in genic regions compared to gene deserts. The consequence of which, is that their integration has greater potential to have affects on gene regulation. The sequences of SVAs show potential for the formation of secondary structure including G-quadruplex DNA. We have shown that the human specific SVA subtypes (E-F1) show the greatest potential for forming G-quadruplexes within the central tandem repeat component in addition to the 5’ ‘CCCTCT’ hexamer. We undertook a detailed analysis of the PARK7 SVA D, located in the promoter of the PARK7 gene (also termed DJ-1), in a HapMap cohort where we identified 2 variable number tandem repeat domains and 1 tandem repeat within this SVA with the 5’ CCCTCT element being one of the variable regions. Functionally we were able to demonstrate that this SVA contains multiple regulatory elements that support reporter gene expression in vitro and further show these elements exhibit orientation dependency.

Conclusions

Our data supports the hypothesis that SVAs integrate preferentially in to open chromatin where they could modify the existing transcriptional regulatory domains or alter expression patterns by a variety of mechanisms.

Keywords:
SVA; PARK7; DJ-1; Genetic variation; G-quadruplex DNA; Retrotransposon