Reorganization of 3D genome architecture provides insights into pathogenesis of early fatty liver disease in laying hens

Yanli Liu ¹Zhuqing Zheng ²Chaohui Wang ¹Yumeng Wang ¹Xi Sun ¹Zhouzheng Ren ¹Xin Yang ¹Xiaojun Yang¹

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作者信息

1. College of Animal Science and Technology,Northwest A&F University,Yangling 712100,China
2. Institute of Agricultural Biotechnology,Jingchu University of Technology,Jingmen 448000,China
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Abstract

Background Fatty liver disease causes huge economic losses in the poultry industry due to its high occurrence and lethality rate.Three-dimensional(3D)chromatin architecture takes part in disease processing by regulating tran-scriptional reprogramming.The study is carried out to investigate the alterations of hepatic 3D genome and H3K27ac profiling in early fatty liver(FLS)and reveal their effect on hepatic transcriptional reprogramming in laying hens.Results Results show that FLS model is constructed with obvious phenotypes including hepatic visible lipid deposi-tion as well as higher total triglyceride and cholesterol in serum.A/B compartment switching,topologically associat-ing domain(TAD)and chromatin loop changes are identified by high-throughput/resolution chromosome conforma-tion capture(HiC)technology.Targeted genes of these alternations in hepatic 3D genome organization significantly enrich pathways related to lipid metabolism and hepatic damage.H3K27ac differential peaks and differential expres-sion genes(DEGs)identified through RNA-seq analysis are also enriched in these pathways.Notably,certain DEGs are found to correspond with changes in 3D chromatin structure and H3K27ac binding in their promoters.DNA motif analysis reveals that candidate transcription factors are implicated in regulating transcriptional reprogram-ming.Furthermore,disturbed folate metabolism is observed,as evidenced by lower folate levels and altered enzyme expression.Conclusion Our findings establish a link between transcriptional reprogramming changes and 3D chromatin struc-ture variations during early FLS formation,which provides candidate transcription factors and folate as targets for FLS prevention or treatment.

Key words

3D chromatin architecture/Fatty liver disease/Folate/H3K27ac profiling/Transcription reprogramming

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基金项目

National Science Foundation of China(32372910)

National Science Foundation of China(32102567)

Program for Shaanxi Science & Technology(2022KJXX-13)

Program for Shaanxi Science & Technology(2023-YBNY-144)

Program for Shaanxi Science & Technology(K3031223077)

Program for Shaanxi Science & Technology(2022GD-TSLD-46-0302)

出版年

2024

畜牧与生物技术杂志(英文版)

中国科学技术协会

畜牧与生物技术杂志(英文版)

CSTPCD

影响因子：0.765

ISSN：1674-9782

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