Genomics & Informatics

Korea Genome Organization (한국유전체학회)
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Cell line-specific features of 3D chromatin organization in hepatocellular carcinoma

  • Yeonwoo Kim (Department of Biological Sciences, Korea Advanced Institute of Science and Technology) ;
  • Hyeokjun Yang (Department of Biological Sciences, Korea Advanced Institute of Science and Technology) ;
  • Daeyoup Lee (Department of Biological Sciences, Korea Advanced Institute of Science and Technology)
  • Received : 2023.03.13
  • Accepted : 2023.04.14
  • Published : 2023.06.30
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Abstract

Liver cancer, particularly hepatocellular carcinoma (HCC), poses a significant global threat to human lives. To advance the development of innovative diagnostic and treatment approaches, it is essential to examine the hidden features of HCC, particularly its 3D genome architecture, which is not well understood. In this study, we investigated the 3D genome organization of four HCC cell lines-Hep3B, Huh1, Huh7, and SNU449-using in situ Hi-C and assay for transposase-accessible chromatin sequencing. Our findings revealed that HCC cell lines had more long-range interactions, both intra-and interchromosomal, compared to human mammary epithelial cells (HMECs). Unexpectedly, HCC cell lines displayed cell line-specific compartmental modifications at the megabase (Mb) scale, which could potentially be leveraged in determining HCC subtypes. At the sub-Mb scale, we observed decreases in intra-TAD (topologically associated domain) interactions and chromatin loops in HCC cell lines compared to HMECs. Lastly, we discovered a correlation between gene expression and the 3D chromatin architecture of SLC8A1, which encodes a sodium-calcium antiporter whose modulation is known to induce apoptosis by comparison between HCC cell lines and HMECs. Our findings suggest that HCC cell lines have a distinct 3D genome organization that is different from those of normal and other cancer cells based on the analysis of compartments, TADs, and chromatin loops. Overall, we take this as evidence that genome organization plays a crucial role in cancer phenotype determination. Further exploration of epigenetics in HCC will help us to better understand specific gene regulation mechanisms and uncover novel targets for cancer treatment.

Keywords

Acknowledgement

We sincerely thank Professor Kyung Hyun Yoo of Sookmyung Women's University for providing the four HCC cell lines, which were instrumental in this work. This research was supported by a National Research Foundation (NRF) grant funded by the Korean government (MSIT) (No. 2022R1A2C3003115) and by an NRF grant funded by the Ministry of Science and ICT (MSIT) (2018R1A5A1024261, SRC).

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