Molecules and Cells

Korean Society for Molecular and Cellular Biology (한국분자세포생물학회)
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The Chromatin Accessibility Landscape of Nonalcoholic Fatty Liver Disease Progression

  • Kang, Byeonggeun (Department of Biological Sciences, Institute of Molecular Biology & Genetics, Seoul National University) ;
  • Kang, Byunghee (Department of Life Sciences, Pohang University of Science and Technology (POSTECH)) ;
  • Roh, Tae-Young (Department of Life Sciences, Pohang University of Science and Technology (POSTECH)) ;
  • Seong, Rho Hyun (Department of Biological Sciences, Institute of Molecular Biology & Genetics, Seoul National University) ;
  • Kim, Won (Department of Internal Medicine, SMG-SNU Boramae Medical Center, Seoul National University College of Medicine)
  • Received : 2022.01.03
  • Accepted : 2022.01.10
  • Published : 2022.05.31
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Abstract

The advent of the assay for transposase-accessible chromatin using sequencing (ATAC-seq) has shown great potential as a leading method for analyzing the genome-wide profiling of chromatin accessibility. A comprehensive reference to the ATAC-seq dataset for disease progression is important for understanding the regulatory specificity caused by genetic or epigenetic changes. In this study, we present a genome-wide chromatin accessibility profile of 44 liver samples spanning the full histological spectrum of nonalcoholic fatty liver disease (NAFLD). We analyzed the ATAC-seq signal enrichment, fragment size distribution, and correlation coefficients according to the histological severity of NAFLD (healthy control vs steatosis vs fibrotic nonalcoholic steatohepatitis), demonstrating the high quality of the dataset. Consequently, 112,303 merged regions (genomic regions containing one or multiple overlapping peak regions) were identified. Additionally, we found differentially accessible regions (DARs) and performed transcription factor binding motif enrichment analysis and de novo motif analysis to determine new biomarker candidates. These data revealed the gene-regulatory interactions and noncoding factors that can affect NAFLD progression. In summary, our study provides a valuable resource for the human epigenome by applying an advanced approach to facilitate diagnosis and treatment by understanding the non-coding genome of NAFLD.

Keywords

Acknowledgement

This research was supported by the Collaborative Genome Program for Fostering New Post-Genome Industry of the National Research Foundation (NRF) and funded by the Ministry of Science and ICT (MIST) (NRF-2017M3C9A6044199) (R.H.S.). This work was supported by the National Research Foundation of Korea grant funded by the Korea government (MEST) (2021R1A2C2005820, 2021M3A9E4021818) (W.K.).

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