Three-dimensional geome study of procine livers during development and metabolic adaptation

ABSTRACT: Liver development and metabolic adaptation are well-orchestrated by a series of signaling pathways and genes. Chromatin architecture is known to influence gene expression, yet its role in controlling liver development and metabolism remains unclear. We performed high-throughput chromatin conformation capture sequencing (HiC-seq) and integrated RNA sequencing (RNA-seq) and chromatin immunoprecipitation sequencing (ChIP-seq) on liver tissue that were collected from six key developmental stages (embryonic day 38 [E38] – 2 years [2y]) and a high fat diet (HFD) feeding group. Our data revealed global three-dimensional (3D) reorganization during liver development from the scales of compartment, topologically associated domain (TAD) and promoter-enhancer interaction (PEI), which consistently affects the expression level of genes known to be important for liver development and function. Comparison of 3D genome and gene expression profiles between pig liver development and human hepatocellular carcinoma (HCC) revealed similarities between fatal liver and HCC and provided potential explanation for the aberrant expression in HCC from the perspective of chromatin architecture. Moreover, the similar genome architecture and expression of genes related to lipid metabolism between nomally and HFD feeding pigs, along with the thicker back fat in HFD feeding pigs compared to normally feeding pigs, supported that pigs are resistant to nonalcoholic fatty liver disease (NAFLD). Together, our results provide a global view of dynamic chromatin interactions during liver development and metabolic adaptation induced by HFD feeding, which may open new avenues for liver research and HCC therapeutic interventions.

ORGANISM(S): Sus scrofa

PROVIDER: GSE176387 | GEO | 2022/03/15

REPOSITORIES: GEO