Table_1_Genome-Wide Analysis on the Landscape of Transcriptomes and Their Relationship With DNA Methylomes in the Hypothalamus Reveals Genes Related to Sexual Precocity in Jining Gray Goats.XLSX

The Jining Gray goat is famous for its sexual precocity; however, the exact regulatory mechanism is still unknown. The hypothalamus is the key centrum in the process of animal reproduction, especially in signal transduction, and the initiation of puberty. The identification of potential genes and pathways in the hypothalamus of Jining Gray goat is critical to understanding the regulatory mechanism of sexual precocity in these goats. In this study, mRNA transcriptome analysis of the hypothalamus of juvenile and pubertal goats revealed eight genes (NTS, ADORA1, CRH, UCN3, E2F2, PDGFRB, GNRH1, and CACNA1C) and three pathways [neuroactive ligand-receptor interaction; gonadotropin-releasing hormone (GnRH) signal; melanoma] that are involved in this regulation. Subsequent methylation analysis on differentially methylated region (DMR) genes revealed the potential regulation network that influences pubertal onset. Correlation analysis verified the methylation level of some DMR genes correlates negatively with expression level. Integrated analysis between transcriptomes and methylomes identified 80 candidate genes involved in GnRH and neuroactive ligand signal pathways, of which CACNA1C and CRH were differentially expressed genes (DEGs) influenced by methylation level. The GnRH gene was the only DEG not affected by its methylation level. In summary, in this study, we identified eight genes and three pathways that are related to pubertal onset in Jining Gray goats, and the expression of CACNA1C and CRH genes of the GnRH and neuroactive ligand signal pathways were influenced by DNA methylation, while that of the GnRH gene was not affected.

济宁青山羊（Jining Gray goat）以性早熟（sexual precocity）著称，但其确切的调控机制仍未阐明。下丘脑（hypothalamus）是动物生殖过程中的关键中枢，尤其在信号转导及青春期启动进程中发挥核心作用。鉴定济宁青山羊下丘脑中的潜在基因与调控通路，对解析其性早熟的分子调控机制至关重要。本研究对幼年及青春期山羊的下丘脑开展mRNA转录组（mRNA transcriptome）分析，筛选得到8个参与该调控过程的基因（NTS、ADORA1、CRH、UCN3、E2F2、PDGFRB、GNRH1及CACNA1C）以及3条相关通路：神经活性配体-受体相互作用通路、促性腺激素释放激素（GnRH）信号通路、黑色素瘤通路。后续针对差异甲基化区域（differentially methylated region, DMR）基因开展甲基化分析，揭示了影响青春期启动的潜在调控网络。相关性分析证实，部分DMR基因的甲基化水平与mRNA表达水平呈显著负相关。转录组（transcriptome）与甲基化组（methylome）整合分析共鉴定出80个参与GnRH及神经活性配体信号通路的候选基因，其中CACNA1C与CRH为受甲基化水平调控的差异表达基因（differentially expressed genes, DEGs）。GNRH1基因是唯一不受自身甲基化水平调控的差异表达基因。综上，本研究鉴定出与济宁青山羊青春期启动相关的8个基因及3条通路，且GnRH及神经活性配体信号通路中的CACNA1C与CRH基因的表达受DNA甲基化调控，而GNRH1基因的表达则不受该调控方式影响。