The Regulation of Monoamine Oxidase A Gene Expression by Distinct Variable Number Tandem Repeats

AbstractThe 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) forMAOA, 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 twoMAOA 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 twoMAOA isoforms was differentially modulated by the two VNTRs located in the promoter region. The most extensively studied uVNTR, previously considered a positive regulator of theMAOA 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 abundantMAOA isoform. The haplotype analysis for these two VNTRs demonstrated a bias against the presence of ...
Source: Journal of Molecular Neuroscience - Category: Neuroscience Source Type: research