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. 2013 May 23:7:83.
doi: 10.3389/fnins.2013.00083. eCollection 2013.

Epigenetic regulation of the oxytocin receptor gene: implications for behavioral neuroscience

Robert Kumsta  1 , Elisabeth Hummel, Frances S Chen, Markus Heinrichs
Affiliations

Epigenetic regulation of the oxytocin receptor gene: implications for behavioral neuroscience

Robert Kumsta et al. Front Neurosci. .

Abstract

Genetic approaches have improved our understanding of the neurobiological basis of social behavior and cognition. For instance, common polymorphisms of genes involved in oxytocin signaling have been associated with sociobehavioral phenotypes in healthy samples as well as in subjects with mental disorders. More recently, attention has been drawn to epigenetic mechanisms, which regulate genetic function and expression without changes to the underlying DNA sequence. We provide an overview of the functional importance of oxytocin receptor gene (OXTR) promoter methylation and summarize studies that have investigated the role of OXTR methylation in behavioral phenotypes. There is first evidence that OXTR methylation is associated with autism, high callous-unemotional traits, and differential activation of brain regions involved in social perception. Furthermore, psychosocial stress exposure might dynamically regulate OXTR. Given evidence that epigenetic states of genes can be modified by experiences, especially those occurring in sensitive periods early in development, we conclude with a discussion on the effects of traumatic experience on the developing oxytocin system. Epigenetic modification of genes involved in oxytocin signaling might be involved in the mechanisms mediating the long-term influence of early adverse experiences on socio-behavioral outcomes.

Keywords: autistic disorder; epigenetics; methylation; oxytocin receptor gene; social neuroscience.

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Figures

Figure 1
Figure 1
Panel (A) (top) shows the genomic organization of the oxytocin receptor gene (OXTR). The OXTR gene is located on chromosome 3p25–3p26.2, spans 17 kb, and contains three introns and four exons, indicated by boxes. The protein-coding region is indicated in gray (ATG denotes the transcription start site, and TGA denotes the stop codon). The enlarged section at the bottom of panel (A) shows the location of a CpG island, which spans exon 1 through exon 3. The genomic region investigated by Kusui et al. with regard to methylation effects on gene expression is indicated by the narrow box. The MT2 region in particular (shown in black) was shown to be functionally significant for OXTR gene regulation (see text). Panel (B) shows the regions within the CpG island that were investigated with regard to differential methylation. Filled circles indicate individual CpG sites with significant differences in methylation levels. Numbering is relative to the translation start site (+1).
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