Dysregulated H3K27 Acetylation Is Implicated in Fatty Liver Hemorrhagic Syndrome in Chickens

Abstract

Epigenetic regulation of gene expression has been reported in the pathogenesis of metabolic disorders such as diabetes and liver steatosis in humans. However, the molecular mechanisms of fatty liver hemorrhagic syndrome (FLHS) in chickens have been rarely studied. H3K27ac chromatin immunoprecipitation coupled with high-throughput sequencing and high-throughput RNA sequencing was performed to compare genome-wide H3K27ac profiles and transcriptomes of liver tissue between healthy and FLHS chickens. In total, 1,321 differential H3K27ac regions and 443 differentially expressed genes were identified (| log2Fold change| ≥ 1 and P-value ≤ 0.05) between the two groups. Binding motifs for transcription factors involved in immune processes and metabolic homeostasis were enriched among those differential H3K27ac regions. Differential H3K27ac peaks were associated with multiple known FLHS risk genes, involved in lipid and energy metabolism (PCK1, APOA1, ANGPTL4, and FABP1) and the immune system (FGF7, PDGFRA, and KIT). Previous studies and our current results suggested that the high-energy, low-protein (HELP) diet might have an impact on histone modification and chromatin structure, leading to the dysregulation of candidate genes and the peroxisome proliferator-activated receptor (PPAR) signaling pathway, which causes excessive accumulation of fat in the liver tissue and induces the development of FLHS. These findings highlight that epigenetic modifications contribute to the regulation of gene expression and play a central regulatory role in FLHS. The PPAR signaling pathway and other genes implicated in FLHS are of great importance for the development of novel and specific therapies for FLHS-susceptible commercial laying hens.

Genome analysis reveals hepatic transcriptional reprogramming changes mediated by enhancers during chick embryonic development

“…Previous study reported that great changes genome-wide H3K27ac profiles changed a lot in the liver of FLHS chicks ( Zhu et al, 2020 ). Consistent with the results in the present study, hepatic total H3K27ac and H3K4me2 levels were different among 3 embryonic days.…”

Osteocalcin and Its Potential Functions for Preventing Fatty Liver Hemorrhagic Syndrome in Poultry

“…Similar to its function in mammals [ 115 ], PPARα exerts function in regulating the related pathways with lipid-lowering effect in chickens [ 16 , 123 ]. The activation of PPARα is suppressed in FLHS chickens [ 124 , 125 ]. Chen et al [ 124 ] cloned and synthesized PPARα protein for producing chicken polyclonal antibodies and showed that the expression of PPARα was decreased in FLHS chickens.…”

“…Chen et al [ 124 ] cloned and synthesized PPARα protein for producing chicken polyclonal antibodies and showed that the expression of PPARα was decreased in FLHS chickens. Zhu et al [ 125 ] reported that high energy and low protein diet (HELP), one of the natural causes of chicken FLHS, dysregulated the PPARα signaling pathway, causing excessive accumulation of fat in the liver tissue with the potential to develop FLHS in chickens.…”

Roles of Estrogens in the Healthy and Diseased Oviparous Vertebrate Liver

“…A widespread H3K27ac dysregulation in the liver of FLHS-affected chickens was observed, and FLHS-associated variations in H3K27ac marks were associated with known FLHS risk genes involved in lipid and energy metabolism ( pck1 , apoa1 , angptl4 , and fabp1 ) and immune function ( fgf7 , pdgfra , and kit ). Furthermore, the PPAR signaling pathway was most significantly enriched in FLHS [ 162 ]. Interestingly, this pathway was also highlighted in an integrated analysis of the methylome and transcriptome in FLHS chicken.…”