Functionally Antagonistic Transcription Factors IRF1 and IRF2 Regulate the Transcription of the Dopamine Receptor D2 Gene Associated with Aggressive Behavior of Weaned Pigs

SIMPLE SUMMARY: Aggressive behavior in pigs after mixing is an issue of animal welfare. This trial was conducted to evaluate the impact of the dopamine receptor (DR) D2 gene on aggressive behavior in pigs. We found that the core promoter region of the DRD2 gene is located in −2212~−1127 bp. A single-nucleotide polymorphism, rs1110730503, for the DRD2 gene is associated with aggressive behavior in pigs and influences the binding of the transcriptional factor interferon regulatory factor (IRF) 2. The transcriptional factor IRF1 upregulates the expression of the DRD2 gene; however, IRF2 downregulates the gene’s expression. IRF1 and IRF2 are functionally antagonistic to each other. Aggressive behavior in pigs is impacted by the DRD2 gene and its expression. These results provide insight into the genetics and neurophysiology of aggressive behavior in pigs. ABSTRACT: Aggressive behavior has negative effects on animal welfare and growth performance in pigs. The dopamine receptor D2 (DRD2) has a critical neuromodulator role in the dopamine signal pathway within the brain to control behavior. A functional single-nucleotide polymorphism (SNP), rs1110730503, in the promoter region of the porcine DRD2 gene was identified, which affects aggressive behavior in pigs. A chromatin immunoprecipitation (ChIP) assay was used to identify the interactions between interferon regulatory factor 1 (IRF1) and IRF2 with the DRD2 gene. The overexpression or knockdown of these two transcription factors in porcine kidney-15 (PK15) and porcine neuronal cells (PNCs) indicate that the binding of IRF1 to DRD2 promotes the transcription of the DRD2 gene, but the binding of IRF2 to the DRD2 gene inhibits its transcription. Furthermore, IRF1 and IRF2 are functionally antagonistic to each other. The downregulation of DRD2 or upregulation of IRF2 increased the apoptosis rate of porcine neuroglial cells. Taken together, we found that transcriptional factors IRF1 and IRF2 have vital roles in regulating the transcription of the DRD2 gene, and rs1110730503 (−915A/T) is a functional SNP that influences IRF2 binding to the promoter of the DRD2 gene. These findings will provide further insight towards controlling aggressive behavior in pigs.