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.