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Background <p>Endometrial receptivity (ERE) is a transient uterine state that determines the success of blastocyst implantation; however, the epigenomic regulation underlying ERE establishment in goats remains unclear. Here, we profiled transcriptional and epigenomic features of endometrial tissues from pregnant goats during the peri-implantation window and nonpregnant control goats in the regressed luteal phase to uncover the transcriptional regulatory networks responsible for ERE establishment in goats, utilizing RNA-seq, ATAC-seq, and H3K27ac CUT&amp;Tag.</p> Results <p>A total of 3,143 differentially expressed genes (DEGs) were identified, accompanied by significant alterations in chromatin accessibility and H3K27ac modifications between receptive and non-receptive endometria. The targeted genes associated with these epigenetic changes were significantly enriched in pathways related to cell adhesion, immune tolerance, and embryo attachment. Motif enrichment and transcription factor (TF) footprinting analyses identified members of the FOS/JUN, SOX, HNF1, CEBP, and BATF families as candidate regulators, implicating downstream genes involved in ERE establishment, including <i>SPP1</i>, <i>FOXO1</i>, <i>KLF4/6</i>, <i>STAT1</i>, <i>IFI6</i>, <i>ITGB8</i>, <i>PLAC8</i>, <i>DUSP4</i>, <i>NR1D1</i>, <i>ISG15</i>, <i>RUFY4</i>, and <i>PIK3R3</i>. In addition, numerous super-enhancers were identified, indicating regions of high regulatory activity and potential long-range gene-enhancers interactions in the endometrium. Integration of multi-omics datasets revealed a strong correlation (<i>r</i> &gt; 0.7) among chromatin accessibility, H3K27ac activation, and the expression of 172 DEGs. Furthermore, a set of hub genes (<i>KLF6</i>, <i>IFI6</i>, <i>MCL1</i>, <i>SDC4</i>, <i>SUSD6</i>, <i>MAFF</i>, and <i>IL6R</i>) that appear to coordinate TF binding and distal super-enhancers activity associated with ERE establishment.</p> Conclusions <p>Our data provided an integrated epigenomic atlas of endometrial receptivity establishment in goats and identify candidate regulatory elements and transcription factors that may orchestrate uterine preparation for implantation. These findings offer valuable insights and testable targets for improving fertility in ruminant livestock.</p>

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

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年1月9日

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  • Zhipeng Sun,
  • Junyin Zhao,
  • Yuhao Liao,
  • Yuqin Cheng,
  • Houmo Yu,
  • Mingming Wang,
  • Xingqiang Fang,
  • Songjian Yang,
  • Yongju Zhao

摘要

Background

Endometrial receptivity (ERE) is a transient uterine state that determines the success of blastocyst implantation; however, the epigenomic regulation underlying ERE establishment in goats remains unclear. Here, we profiled transcriptional and epigenomic features of endometrial tissues from pregnant goats during the peri-implantation window and nonpregnant control goats in the regressed luteal phase to uncover the transcriptional regulatory networks responsible for ERE establishment in goats, utilizing RNA-seq, ATAC-seq, and H3K27ac CUT&Tag.

Results

A total of 3,143 differentially expressed genes (DEGs) were identified, accompanied by significant alterations in chromatin accessibility and H3K27ac modifications between receptive and non-receptive endometria. The targeted genes associated with these epigenetic changes were significantly enriched in pathways related to cell adhesion, immune tolerance, and embryo attachment. Motif enrichment and transcription factor (TF) footprinting analyses identified members of the FOS/JUN, SOX, HNF1, CEBP, and BATF families as candidate regulators, implicating downstream genes involved in ERE establishment, including SPP1, FOXO1, KLF4/6, STAT1, IFI6, ITGB8, PLAC8, DUSP4, NR1D1, ISG15, RUFY4, and PIK3R3. In addition, numerous super-enhancers were identified, indicating regions of high regulatory activity and potential long-range gene-enhancers interactions in the endometrium. Integration of multi-omics datasets revealed a strong correlation (r > 0.7) among chromatin accessibility, H3K27ac activation, and the expression of 172 DEGs. Furthermore, a set of hub genes (KLF6, IFI6, MCL1, SDC4, SUSD6, MAFF, and IL6R) that appear to coordinate TF binding and distal super-enhancers activity associated with ERE establishment.

Conclusions

Our data provided an integrated epigenomic atlas of endometrial receptivity establishment in goats and identify candidate regulatory elements and transcription factors that may orchestrate uterine preparation for implantation. These findings offer valuable insights and testable targets for improving fertility in ruminant livestock.