Genome-wide profiling of histone acetylation enhancer of fatty liver hemorrhagic syndrome in laying hens

¹Department of Pathophysiology, Anhui Medical University, Hefei, 230032, China
²Laboratory Animal Research Center, College of Basic Medical Science, Anhui Medical University, Hefei, 230032, China

Correspondence: Yunshu Tang,Email: tangyunshu0106@163.com
Yaling Zhu, Tel: +86-15970427865, Fax: +86-15970427865, Email: zhuyaling@ahmu.edu.cn

Received: 18 October 2023 • Revised: 31 January 2024 • Accepted: 18 February 2024

Abstract

Objective
Rare study of the non-coding and regulatory regions of the genome limits our ability to decode the mechanisms of fatty liver hemorrhage syndrome (FLHS) in chickens. Method: Herein, we constructed the HFD-induced FLHS chicken model to investigate the genome-wide active enhancers and transcriptome by H3K27ac target chromatin immunoprecipitation sequencing (ChIP-seq) and RNA sequencing (RNA-Seq) profiles of normal and FLHS liver tissues. Concurrently, an integrative analysis combining ChIP-seq with RNA-Seq and a comparative analysis with chicken FLHS, rat Non-alcoholic fatty liver disease (NAFLD) and human NAFLD at the transcriptome level revealed the enhancer target genes and conservative genes involved in metabolic processes.
Results
In total, 56 and 199 peak-genes were identified in upregulated peak-genes positively regulated by H3K27ac (Cor (peak-gene correlation) ≥ 0.5 & log2(FoldChange) ≥ 1) (PP) and downregulated peak-genes positively regulated by H3K27ac (Cor (peak-gene correlation) ≥ 0.5 & log2(FoldChange) ≤ -1)(PN), respectively; then we screened key regulatory targets mainly distributing in lipid metabolism (PCK1, APOA4, APOA1, INHBE) and apoptosis (KIT, NTRK2) together with MAPK and PPAR signaling pathway in FLHS. Intriguingly, PCK1 was also significantly covered in up-regulated super-enhancers (SEs), which further implied the vital role of PCK1 during the development of FLHS.
Conclusion
Together, our studies provided new insights into the pathogenesis and potential therapy biomarkers of FLHS.

Keywords: ChIP-Seq; H3K27ac; RNA-Seq; Fatty Liver Hemorrhagic Syndrome; Super-enhancer