整合 3D 基因组学、多组学分析以及遗传调控机制的功能验证,研究鸡腹部脂肪沉积的机制。
Integrative 3D genomics with multi-omics analysis and functional validation of genetic regulatory mechanisms of abdominal fat deposition in chickens.
机构信息
College of Animal Science and Technology, Northeast Agricultural University, Harbin, 150030, PR China.
Key Laboratory of Chicken Genetics and Breeding, Ministry of Agriculture and Rural Affairs, Harbin, 150030, PR China.
出版信息
Nat Commun. 2024 Oct 28;15(1):9274. doi: 10.1038/s41467-024-53692-6.
Chickens are the most abundant agricultural animals globally, with controlling abdominal fat deposition being a key objective in poultry breeding. While GWAS can identify genetic variants associated with abdominal fat deposition, the precise roles and mechanisms of these variants remain largely unclear. Here, we use male chickens from two lines divergently selected for abdominal fat deposition as experimental models. Through the integration of genomic, epigenomic, 3D genomic, and transcriptomic data, we build a comprehensive chromatin 3D regulatory network map to identify the genetic regulatory mechanisms that influence abdominal fat deposition in chickens. Notably, we find that the rs734209466 variant functions as an allele-specific enhancer, remotely enhancing the transcription of IGFBP2 and IGFBP5 by the binding transcription factor IRF4. This interaction influences the differentiation and proliferation of preadipocytes, which ultimately affects phenotype. This work presents a detailed genetic regulatory map for chicken abdominal fat deposition, offering molecular targets for selective breeding.
鸡是全球数量最多的农业动物,控制腹部脂肪沉积是家禽养殖的一个关键目标。虽然全基因组关联分析 (GWAS) 可以识别与腹部脂肪沉积相关的遗传变异,但这些变异的确切作用和机制在很大程度上仍不清楚。在这里,我们使用两个腹部脂肪沉积差异选择的雄性鸡系作为实验模型。通过整合基因组、表观基因组、3D 基因组和转录组数据,我们构建了一个全面的染色质 3D 调控网络图谱,以鉴定影响鸡腹部脂肪沉积的遗传调控机制。值得注意的是,我们发现 rs734209466 变异作为一个等位基因特异性增强子起作用,通过结合转录因子 IRF4 远程增强 IGFBP2 和 IGFBP5 的转录。这种相互作用影响前脂肪细胞的分化和增殖,最终影响表型。这项工作为鸡腹部脂肪沉积提供了详细的遗传调控图谱,为选择性育种提供了分子靶标。