Tissue-Specific Chromatin Accessibility Regions and Transcription Factor Binding Sites in Pig Brain and Endocrine Tissues

Abstract

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.

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