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

Jing Zhao,Allan P Schinckel,Meng Cheng,Yanli Guo,Qinglei Xu,Bo Zhou,Chunlei Zhang,Mingzheng Liu,Siyuan Gao,Xianle Zhao

doi:10.3390/biology11010135

Jing Zhao, Allan P Schinckel + Show 8 more

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https://doi.org/10.3390/biology11010135

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Journal: Biology	Publication Date: Jan 14, 2022
Citations: 2	License type: CC BY 4.0

Affiliation: Nanjing Agricultural University

Abstract

Simple SummaryAggressive 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.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.

Highlights

To improve the efficiency of space utilization and management, regrouping is a common practice in intensive pig farms [1]
The objective of this study is to identify the single-nucleotide polymorphism (SNP) of the dopamine receptor D2 (DRD2) gene that are involved in the regulation of interferon regulatory factor 1 (IRF1) and interferon regulatory factor 2 (IRF2) binding, as well as to explore the molecular regulation mechanism of the DRD2 gene
The sequence (2250 bp) on the upstream of the porcine DRD2 gene was used for the prediction of the promoter, transcription factor binding sites, and CpG islands

Summary

Introduction

To improve the efficiency of space utilization and management, regrouping is a common practice in intensive pig farms [1]. Because pigs are social animals, unfamiliar pigs often fight with each other after mixing to obtain feed, space, and other resources until a new social hierarchy has been reestablished [1]. A previous study showed that growth traits were related to behavioral traits in pigs [2]. In recent decades commercial pig breeds have increasingly become more aggressive with selection for increased growth performance [3]. Aggressive behavior causes serious physical injury to pigs, increases the risk of disease, and reduces the level of animal welfare [4]. Since aggressive behavior traits are difficult to assess for breeding selection in commercial pig farms, one alternative means of reducing aggressive behavior is to identify and select pigs based on molecular genetic markers of aggressive behavior [5,6]

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