The regulation of monoamine oxidase A gene expression by distinct variable number tandem repeats

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dc.contributor.author Manca, Maurizio
dc.contributor.author Pessoa, Veridiana
dc.contributor.author Lopez, Ana Illera
dc.contributor.author Harrison, Patrick T.
dc.contributor.author Miyajima, Fabio
dc.contributor.author Sharp, Helen
dc.contributor.author Pickles, Andrew
dc.contributor.author Hill, Jonathan
dc.contributor.author Murgatroyd, Chris
dc.contributor.author Bubb, Vivien J.
dc.contributor.author Quinn, John P.
dc.date.accessioned 2018-06-15T11:47:13Z
dc.date.available 2018-06-15T11:47:13Z
dc.date.issued 2018
dc.identifier.citation Manca, M., Pessoa, V., Lopez, A. I., Harrison, P. T., Miyajima, F., Sharp, H., Pickles, A., Hill, J., Murgatroyd, C., Bubb, V. J. and Quinn, J. P. (2018) 'The regulation of monoamine oxidase A gene expression by distinct variable number tandem repeats', Journal of Molecular Neuroscience, 64(3), pp. 459-470. doi: 10.1007/s12031-018-1044-z en
dc.identifier.volume 64
dc.identifier.issued 3
dc.identifier.startpage 459
dc.identifier.endpage 470
dc.identifier.issn 0895-8696
dc.identifier.uri http://hdl.handle.net/10468/6336
dc.identifier.doi 10.1007/s12031-018-1044-z
dc.description.abstract The monoamine oxidase A (MAOA) uVNTR (upstream variable number tandem repeat) is one of the most often cited examples of a gene by environment interaction (GxE) in relation to behavioral traits. However, MAOA possesses a second VNTR, 500 bp upstream of the uVNTR, which is termed d- or distal VNTR. Furthermore, genomic analysis indicates that there are a minimum of two transcriptional start sites (TSSs) for MAOA, one of which encompasses the uVNTR within the 5' untranslated region of one of the isoforms. Through expression analysis in semi-haploid HAP1 cell lines genetically engineered in order to knockout (KO) either the uVNTR, dVNTR, or both VNTRs, we assessed the effect of the two MAOA VNTRs, either alone or in combination, on gene expression directed from the different TSSs. Complementing our functional analysis, we determined the haplotype variation of these VNTRs in the general population. The expression of the two MAOA isoforms was differentially modulated by the two VNTRs located in the promoter region. The most extensively studied uVNTR, previously considered a positive regulator of the MAOA gene, did not modulate the expression of what it is considered the canonical isoform, while we found that the dVNTR positively regulated this isoform in our model. In contrast, both the uVNTR and the dVNTR were found to act as negative regulators of the second less abundant MAOA isoform. The haplotype analysis for these two VNTRs demonstrated a bias against the presence of one of the potential variants. The uVNTR and dVNTR differentially affect expression of distinct MAOA isoforms, and thus, their combined profiling offers new insights into gene-regulation, GxE interaction, and ultimately MAOA-driven behavior. en
dc.description.sponsorship Medical Research Council (G0400577); Wellcome Trust (109095/Z/15/Z) en
dc.format.mimetype application/pdf en
dc.language.iso en en
dc.publisher Humana Press en
dc.relation.uri https://link.springer.com/article/10.1007%2Fs12031-018-1044-z
dc.rights © 2018, the Authors. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. en
dc.rights.uri http://creativecommons.org/licenses/by/4.0/
dc.subject MAOA en
dc.subject Isoforms en
dc.subject VNTR en
dc.subject Gene expression en
dc.subject Transcription en
dc.subject Haplotype en
dc.title The regulation of monoamine oxidase A gene expression by distinct variable number tandem repeats en
dc.type Article (peer-reviewed) en
dc.internal.authorcontactother Patrick Harrison, Physiology, University College Cork, Cork, Ireland. +353-21-490-3000 Email: p.harrison@ucc.ie en
dc.internal.availability Full text available en
dc.description.version Published Version en
dc.contributor.funder Wellcome Trust
dc.contributor.funder Medical Research Council
dc.description.status Peer reviewed
dc.identifier.journaltitle Journal of Molecular Neuroscience en
dc.internal.IRISemailaddress p.harrison@ucc.ie en


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© 2018,  the Authors. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. Except where otherwise noted, this item's license is described as © 2018, the Authors. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.
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