72 / 2026-04-05 15:37:50

A dynamic atlas of 3D genomic architecture during pig development

pig,ChIA-PET,Development

Despite rapid progress in 3D genomics, dynamic maps spanning mammalian development remain limited. Here, we present a comprehensive multi-omics atlas of the pig, comprising 602 datasets across five developmental stages from germ-layer formation to adulthood, integrating ChIP-seq, ATAC-seq, in situ Hi-C, Pol II/CTCF in situ ChIA-PET, and scATAC-seq, with additional multi-omics data from pig kidney xenotransplantation. This atlas defines ~460,000 non-redundant cis-regulatory elements covering 33.55% of the genome, including 8.65% newly annotated regions, substantially expanding existing annotations. At the 3D level, in total 4.73 million chromatin loops were captured, including 0.95 million Pol II loops, 1.36 million CTCF loops, and 2.42 million Hi-C loops. These chromatin loops linked 61.32% of regulatory elements through chromatin interactions and markedly improving resolution.

Based on this atlas, we show that the A/B compartments and TADs remain largely stable after germ-layer differentiation, whereas chromatin loops, particularly long-range interactions, remain highly dynamic and drive compartment switching and boundary repositioning. Tissue-specific and enhancer-enhancer loops contribute to organ-specific gene regulation, with many pre-established during germ-layer differentiation and later repurposed through transcription factor turnover. Additionally, by integrating 3D genome features with epigenomic signals, we predicted the regulatory effects of indels on gene expression, facilitating the prioritization of functional variants for breeding. Cross-species analysis revealed greater conservation of 3D genome organization between pig and human than between mouse and human, with disease-associated variants enriched in conserved regulatory elements. We show that genome rearrangements and activation of pig-specific regulatory elements drive immune gene upregulation after transplantation, whereas interspecies differences in hormone levels impair PPARA-mediated lipid metabolism, compromising renal energy supply and contributing to graft dysfunction. Collectively, we provide a comprehensive pig multi-omics atlas for investigating 3D genome regulation and its roles in development, evolution, and xenotransplantation.