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Korean Society for Biochemistry and Molecular Biology (생화학분자생물학회)
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Vorinostat-induced acetylation of RUNX3 reshapes transcriptional profile through long-range enhancer-promoter interactions in natural killer cells

  • Eun-Chong Lee (Department of Tropical Medicine, Institute of Tropical Medicine, Yonsei University College of Medicine) ;
  • Kyungwoo Kim (Department of Tropical Medicine, Institute of Tropical Medicine, Yonsei University College of Medicine) ;
  • Woong-Jae Jung (Department of Tropical Medicine, Institute of Tropical Medicine, Yonsei University College of Medicine) ;
  • Hyoung-Pyo Kim (Department of Tropical Medicine, Institute of Tropical Medicine, Yonsei University College of Medicine)
  • Received : 2023.03.23
  • Accepted : 2023.05.09
  • Published : 2023.07.31
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Abstract

Natural killer (NK) cells are an essential part of the innate immune system that helps control infections and tumors. Recent studies have shown that Vorinostat, a histone deacetylase (HDAC) inhibitor, can cause significant changes in gene expression and signaling pathways in NK cells. Since gene expression in eukaryotic cells is closely linked to the complex three-dimensional (3D) chromatin architecture, an integrative analysis of the transcriptome, histone profiling, chromatin accessibility, and 3D genome organization is needed to gain a more comprehensive understanding of how Vorinostat impacts transcription regulation of NK cells from a chromatin-based perspective. The results demonstrate that Vorinostat treatment reprograms the enhancer landscapes of the human NK-92 NK cell line while overall 3D genome organization remains largely stable. Moreover, we identified that the Vorinostat-induced RUNX3 acetylation is linked to the increased enhancer activity, leading to elevated expression of immune response-related genes via long-range enhancer-promoter chromatin interactions. In summary, these findings have important implications in the development of new therapies for cancer and immune-related diseases by shedding light on the mechanisms underlying Vorinostat's impact on transcriptional regulation in NK cells within the context of 3D enhancer network.

Keywords

Acknowledgement

This work was supported by the National Research Foundation of Korea (NRF) grants funded by the Korean government (MSIP) (2018M3A9D3079290, 2020R1A2C2013258, and 2022M3A9B6017424 to H.-P. Kim).

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