In diploid mammals, allele-specific three-dimensional (3D) genome architecture may lead to imbalanced gene expression. Through ultradeep in situ Hi-C sequencing of three representative somatic tissues (liver, skeletal muscle, and brain) from hybrid pigs generated by reciprocal crosses of phenotypically and physiologically divergent Berkshire and Tibetan pigs, we uncover extensive chromatin reorganization between homologous chromosomes across multiple scales. Haplotype-based interrogation of multi-omic data revealed the tissue dependence of 3D chromatin conformation, suggesting that parent-of-origin-specific conformation may drive gene imprinting. We quantify the effects of genetic variations and histone modifications on allelic differences of long-range promoter–enhancer contacts, which likely contribute to the phenotypic differences between the parental pig breeds. We also observe the fine structure of somatically paired homologous chromosomes in the pig genome, which has a functional implication genome-wide. This work illustrates how allele-specific chromatin architecture facilitates concomitant shifts in allele-biased gene expression, as well as the possible consequential phenotypic changes in mammals.

中文翻译：

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杂交猪的单倍型解析 3D 染色质结构

在二倍体哺乳动物中，等位基因特异性三维 (3D) 基因组结构可能导致基因表达不平衡。通过对表型和生理上不同的伯克夏猪和藏猪相互杂交产生的杂交猪的三种代表性体细胞组织（肝脏、骨骼肌和大脑）进行超深原位 Hi-C 测序，我们发现了跨多个尺度的同源染色体之间广泛的染色质重组。基于单倍型的多组学数据询问揭示了 3D 染色质构象的组织依赖性，表明亲本特异性构象可能驱动基因印记。我们量化了遗传变异和组蛋白修饰对远程启动子-增强子接触等位基因差异的影响，这可能导致亲本猪品种之间的表型差异。我们还观察到猪基因组中体细胞配对同源染色体的精细结构，这在全基因组范围内具有功能意义。这项工作说明了等位基因特异性染色质结构如何促进等位基因偏向基因表达的伴随变化，以及哺乳动物中可能发生的随之而来的表型变化。