학술논문
Alterations in the hepatocyte epigenetic landscape in steatosis
Document Type
article
Author
Ranjan Kumar Maji; Beate Czepukojc; Michael Scherer; Sascha Tierling; Cristina Cadenas; Kathrin Gianmoena; Nina Gasparoni; Karl Nordström; Gilles Gasparoni; Stephan Laggai; Xinyi Yang; Anupam Sinha; Peter Ebert; Maren Falk-Paulsen; Sarah Kinkley; Jessica Hoppstädter; Ho-Ryun Chung; Philip Rosenstiel; Jan G. Hengstler; Jörn Walter; Marcel H. Schulz; Sonja M. Kessler; Alexandra K. Kiemer
Source
Epigenetics & Chromatin, Vol 16, Iss 1, Pp 1-14 (2023)
Subject
Language
English
ISSN
1756-8935
Abstract
Abstract Fatty 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.