Transomic analysis reveals DNA methylation and transcription factor roles in obese liver protein expression

Obesity impairs hepatic functions through abnormal functional protein expression, potentially through DNA methylation, which suppresses gene expression, and changes in transcription factors (TFs) expression. However, the specific protein expression changes associated with DNA methylation in the obese liver remain unclear. To dissect the relative association of DNA methylome and TF-binding with protein expression changes in the obese liver, we used a trans-omic integration approach combining DNA methylome, transcriptome, proteome, and TF-binding data for the livers of wild-type (WT) and obese (ob/ob) mice. We found that gene and protein expression changes were more strongly associated with TF expression changes than with changes in DNA methylation in promoter region. However, decreased protein expression of the complement and coagulation system in obesity was specifically associated with increased DNA methylation together with decreased expression of TF Hnf4a. Our study highlights abnormal protein expression specifically associated with DNA methylation and TF expression changes in obesity.