Ponsuksili Siriluck, Hadlich Frieder, Trakooljul Nares, Li Shuaichen, Reyer Henry, Oster Michael, Wimmers Klaus
Research Institute for Farm Animal Biology (FBN), Wilhelm-Stahl-Allee 2, 18196, Dummerstorf, Germany.
Faculty of Agricultural and Environmental Sciences, University Rostock, 18059, Rostock, Germany.
Mol Neurobiol. 2025 Jun 7. doi: 10.1007/s12035-025-05128-5.
The cognitive and regulatory processes within higher-order brain structures that regulate the hypothalamic-pituitary-adrenal (HPA) axis and the limbic system orchestrate a complex stress response system. In order to address this, we collected 48 tissue samples from the amygdala (Amy), hippocampus (Hip), thalamus (Tal), hypothalamus (HT), pituitary gland (PG) and adrenal gland (AG). We applied ATAC-seq, a method for profiling accessible chromatin, to map the epigenetic landscape of these brain and endocrine tissues in pigs and generate foundational baseline chromatin accessibility datasets that can serve as a reference for future studies. A total of 321,584 consensus peaks, representing open chromatin regions across various samples and tissues in the pig genome, were identified. Screening for transcription factor binding motifs within these chromatin-accessible regions revealed 377 significantly enriched motifs in at least one tissue (p ≤ 0.001). Among the 93 motifs enriched in only one tissue, some showed concordant expression of their corresponding transcription factors, including GRHL2 and KLF5 in the PG, and GATA4/6, and HAND2 in the AG. Differentially accessible regions (DARs), particularly in promoter regions, between brain and endocrine tissues were identified, with functional specificities in the AG, including cortisol synthesis and secretion, as well as tyrosine metabolism. The cytokine-cytokine receptor interaction and neuroactive ligand-receptor interaction pathways showed greater enrichment and open chromatin accessibility in brain regions compared to endocrine tissues (PG or AG). This study provides valuable insights into brain transcriptional regulation and adds a novel layer of information for future research on genetic improvement and animal welfare.
调节下丘脑 - 垂体 - 肾上腺（HPA）轴和边缘系统的高级脑结构中的认知和调节过程，共同构成了一个复杂的应激反应系统。为了解决这个问题，我们从杏仁核（Amy）、海马体（Hip）、丘脑（Tal）、下丘脑（HT）、垂体（PG）和肾上腺（AG）收集了48个组织样本。我们应用ATAC-seq（一种用于分析可及染色质的方法）来绘制猪这些脑和内分泌组织的表观遗传图谱，并生成基础基线染色质可及性数据集，可为未来研究提供参考。共鉴定出321,584个共有峰，代表猪基因组中各个样本和组织的开放染色质区域。在这些染色质可及区域内筛选转录因子结合基序，发现在至少一个组织中377个基序显著富集（p≤0.001）。在仅在一个组织中富集的93个基序中，一些显示出其相应转录因子的一致表达，包括PG中的GRHL2和KLF5，以及AG中的GATA4/6和HAND2。鉴定了脑和内分泌组织之间的差异可及区域（DAR），特别是在启动子区域，AG中具有功能特异性，包括皮质醇合成和分泌以及酪氨酸代谢。与内分泌组织（PG或AG）相比，细胞因子 - 细胞因子受体相互作用和神经活性配体 - 受体相互作用途径在脑区域显示出更大的富集和开放染色质可及性。本研究为脑转录调控提供了有价值的见解，并为未来的遗传改良和动物福利研究增添了新的信息层面。
