Li Shanglai, Zhao Bingru, Chen Peiyong, Cai Yu, Xu Hui, Yan Chenbo, Wang Feng, Zhang Yanli
Hu Sheep Academy, Nanjing Agricultural University, Nanjing, 210095, China.
Jiangsu Livestock Embryo Engineering Laboratory, Nanjing Agricultural University, Nanjing, 210095, China.
BMC Genomics. 2025 May 20;26(1):508. doi: 10.1186/s12864-025-11621-x.
The pituitary gland, a central regulator of the hypothalamic-pituitary-gonadal (HPG) axis, plays a pivotal role in reproductive efficiency by precisely controlling the secretion of gonadotropins, including follicle-stimulating hormone (FSH) and luteinizing hormone (LH). Chromatin accessibility enables physical interactions between promoters and chromatin-binding factors to drive the gene expression. Despite this mechanistic insight, the chromatin accessibility landscape of the sheep pituitary and its functional implications for reproductive traits remain largely unexplored. To address this knowledge gap, we performed an integrated multi-omics analysis of ATAC-seq and RNA-seq profiling of pituitary from sheep with divergent fecundity phenotypes.
We identified 1,567 differential accessibility regions (DARs) and 768 differentially expressed genes (DEGs). Functional enrichment analysis revealed that the DEGs were significantly associated with key signaling pathways, including neuroactive ligand-receptor interactions, the cAMP signaling pathway, and the calcium signaling pathway, suggesting their critical roles in pituitary-regulated reproductive functions. Based on integrative analysis of ATAC-seq and RNA-seq, we revealed several potentially key genes involved in gonadotropin secretion, such as CMKLR1, TAFA1, and PPP1R17. Furthermore, we identified novel transcription factors (TFs), including NR4A2 and MEF2, which may influence pituitary hormone secretion by modulating chromatin accessibility and gene expression.
This study systematically delineated the gene expression and chromatin accessibility of the pituitary and identified some key regulatory genes associated with gonadotropin secretion in sheep. Our integrated multi-omics analysis identifies critical molecular markers that may contribute to the genetic improvement of reproductive efficiency in ovine species.
垂体作为下丘脑 - 垂体 - 性腺（HPG）轴的中枢调节器，通过精确控制促性腺激素（包括促卵泡激素（FSH）和促黄体生成素（LH））的分泌，在生殖效率中发挥关键作用。染色质可及性使启动子与染色质结合因子之间发生物理相互作用，从而驱动基因表达。尽管有这种机制上的认识，但绵羊垂体的染色质可及性图谱及其对生殖性状的功能影响在很大程度上仍未被探索。为了填补这一知识空白，我们对具有不同繁殖力表型的绵羊垂体进行了ATAC-seq和RNA-seq分析的综合多组学分析。
我们鉴定出1567个差异可及性区域（DARs）和768个差异表达基因（DEGs）。功能富集分析表明，这些DEGs与关键信号通路显著相关，包括神经活性配体 - 受体相互作用、cAMP信号通路和钙信号通路，表明它们在垂体调节的生殖功能中起关键作用。基于ATAC-seq和RNA-seq的综合分析，我们揭示了几个参与促性腺激素分泌的潜在关键基因，如CMKLR1、TAFA1和PPP1R17。此外，我们鉴定出了新的转录因子（TFs），包括NR4A2和MEF2，它们可能通过调节染色质可及性和基因表达来影响垂体激素分泌。
本研究系统地描绘了绵羊垂体的基因表达和染色质可及性，并鉴定出一些与促性腺激素分泌相关的关键调控基因。我们的综合多组学分析确定了可能有助于绵羊生殖效率遗传改良的关键分子标记。
