Transcription and DNA methylation signatures of paternal care in hippocampal dentate gyrus of prairie voles (RNA-Seq)

In socially monogamous prairie voles (Microtus ochrogaster), parental behaviors not only occur in mothers and fathers, but also can exist in virgin males. However, some virgin males display aggressive behaviors towards conspecific pups. Although this behavioral dichotomy in response to pup exposure has been well documented in male virgin voles, little is known about the gene expression changes underlie the parental behavioral differences and their regulatory mechanisms. To address this, we profiled the transcriptome and DNA methylome of hippocampal dentate gyrus of four prairie vole groups, attacker virgin males, parental virgin males, fathers, and mothers. We found a concordant pattern of gene transcription in parental virgin males and fathers, when comparing to the attacker group. The methylome analysis also revealed pathways with genes enriched for epigenetic changes involving both receptor-mediated and secondary messenger signaling across both behavioral phenotypes and sexual experiences. Furthermore, we found correlations between gene expression changes and DNA methylation differences between attacker and parental virgin males, which suggests a canonical gene expression regulatory role of DNA methylation in paternal care. Therefore, our study presents an integrated view of transcriptome and epigenome that provides a DNA epigenetic based molecular insight of paternal behavior. Overall design: Comparative Gene Expression and DNA Methylome profiling of Prairie Vole Dentate Gyrus cells from different groups based on behavioral response to pup-exposure

在社会一夫一妻制的草原田鼠（Microtus ochrogaster）中，亲代抚育行为不仅存在于母鼠与父鼠体内，还可在未交配雄鼠中出现。然而部分未交配雄鼠会对同种幼鼠展现出攻击行为。尽管针对幼崽暴露的行为二分现象已在未交配雄鼠中得到充分记载，但学界对亲代行为差异背后的基因表达变化及其调控机制仍知之甚少。为解决这一科学问题，本研究对四组草原田鼠的海马齿状回组织开展了转录组（transcriptome）与DNA甲基化组（DNA methylome）谱学分析，四组分别为攻击型未交配雄鼠、亲代型未交配雄鼠、父鼠以及母鼠。研究发现，相较于攻击型未交配雄鼠组，亲代型未交配雄鼠与父鼠的基因转录模式高度一致。甲基化组分析还揭示，在两种行为表型与性经历背景下，富集表观遗传变化相关基因的通路同时涵盖受体介导信号通路与第二信使信号通路。此外，本研究发现攻击型与亲代型未交配雄鼠间的基因表达变化与DNA甲基化差异存在相关性，这表明DNA甲基化在父代抚育行为中发挥着经典的基因表达调控作用。因此，本研究整合了转录组与表观基因组（epigenome）数据，为父代行为提供了基于DNA表观遗传的分子层面解析。研究整体设计：基于对幼崽暴露的行为反应，对不同组别草原田鼠的齿状回细胞进行基因表达与DNA甲基化组对比分析。