Multi-omics profiling of chromatin accessibility and H3K27ac reveals super-enhancermediated regulatory networks governing endometrial receptivity in goats

Background Endometrial receptivity (ER), a critical but transient uterine state for successful embryo implantation, remains poorly characterized at the epigenomic level in livestock species. Here, we employed an integrative multi-omics approach to systematically decode the regulatory architecture underlying ER establishment in goats (Capra hircus), combining RNA sequencing (RNA-seq), assay for transposase-accessible chromatin using sequencing (ATAC-seq), and cleavage under targets and tagmentation (CUT&Tag) for H3K27ac profiling. Results Comparative analysis of endometrial tissues at receptive (ER) and non-receptive (CO) stages identified 3,143 differentially expressed genes (DEGs), with significant enrichment in tight junction, focal adhesion, JAK-STAT, MAPK, NF-κB, PI3K-Akt, and AMPK signaling pathways. ATAC-seq revealed pronounced chromatin remodeling, with increased accessibility at promoters of key ER-related genes (SPP1, FOXO1, FOSL2, BMP6, PIK3R3, CLDN3, DUSP1/4, ITGB8, STAT1, FOS, and BMPR1B). Transcription factor (TF) footprinting demonstrated stage-specific occupancy of HNF1A/B, BATF3, and SOX/FOS/JUN family members. Notably, integrative analysis delineated a strong correlation (r > 0.7) between H3K27ac-marked regulatory elements, chromatin accessibility, and 172 DEG expression. Super-enhancer (sEnh) mapping identified FOSL2, KLF6, IFI6, MCL1, SDC4, and IL6R as sEnh-driven hub genes, and confirmed some TFs binding at these loci. Mechanistically, sEnh activation coincided with dynamic H3K27ac deposition and chromatin decompaction, facilitating the recruitment of transcriptional coactivators. Conclusions Collectively, our findings provide the first comprehensive epigenomic atlas of endometrial receptivity in goats and uncover a hierarchical gene regulatory network driven by super-enhancers. This work advances current understanding of the molecular basis of reproductive competence in livestock and offers new targets for enhancing fertility through genetic or epigenetic interventions.