Author:
Maji Ranjan Kumar,Czepukojc Beate,Scherer Michael,Tierling Sascha,Cadenas Cristina,Gianmoena Kathrin,Gasparoni Nina,Nordström Karl,Gasparoni Gilles,Laggai Stephan,Yang Xinyi,Sinha Anupam,Ebert Peter,Falk-Paulsen Maren,Kinkley Sarah,Hoppstädter Jessica,Chung Ho-Ryun,Rosenstiel Philip,Hengstler Jan G.,Walter Jörn,Schulz Marcel H.,Kessler Sonja M.,Kiemer Alexandra K.
Abstract
AbstractFatty liver disease or the accumulation of fat in the liver, has been reported to affect the global population. This comes with an increased risk for the development of fibrosis, cirrhosis, and hepatocellular carcinoma. Yet, little is known about the effects of a diet containing high fat and alcohol towards epigenetic aging, with respect to changes in transcriptional and epigenomic profiles. In this study, we took up a multi-omics approach and integrated gene expression, methylation signals, and chromatin signals to study the epigenomic effects of a high-fat and alcohol-containing diet on mouse hepatocytes. We identified four relevant gene network clusters that were associated with relevant pathways that promote steatosis. Using a machine learning approach, we predict specific transcription factors that might be responsible to modulate the functionally relevant clusters. Finally, we discover four additional CpG loci and validate aging-related differential CpG methylation. Differential CpG methylation linked to aging showed minimal overlap with altered methylation in steatosis.
Funder
Deutsches Zentrum für Herz-Kreislaufforschung
Deutsche Forschungsgemeinschaft
Federal Ministry of Education and Research under the Project Number
Hessian Ministry within the LOEWE Research Initiative ACLF-I
Johann Wolfgang Goethe-Universität, Frankfurt am Main
Publisher
Springer Science and Business Media LLC
Subject
Genetics,Molecular Biology