Genome-Wide Profiling of H3K27ac Identifies TDO2 as a Pivotal Therapeutic Target in Metabolic Associated Steatohepatitis Liver Disease.

ABSTRACT: H3K27ac has been widely recognized as a representative epigenetic marker of active enhancer, while its regulatory mechanisms in pathogenesis of metabolic dysfunction-associated steatotic liver disease (MASLD) remain elusive. Here, a genome-wide comparative study on H3K27ac activities and transcriptome profiling in high fat diet (HFD)-induced MASLD model is performed. A significantly enhanced H3K27ac density with abundant alterations of regulatory transcriptome is observed in MASLD rats. Based on integrative analysis of ChIP-Seq and RNA-Seq, TDO2 is identified as a critical contributor for abnormal lipid accumulation, transcriptionally activated by YY1-promoted H3K27ac. Furthermore, TDO2 depletion effectively protects against hepatic steatosis. In terms of mechanisms, TDO2 activates NF-κB p

SUBMITTER: Zhu Y 

PROVIDER: S-EPMC11615751 | biostudies-literature | 2024 Dec

REPOSITORIES: biostudies-literature