Acute liver steatosis translationally controls the epigenetic regulator MIER1 to promote liver regeneration in a study with male mice

Yanhao Chen (), Lanlan Chen, Xiaoshan Wu, Yongxu Zhao, Yuchen Wang, Dacheng Jiang, Xiaojian Liu, Tingting Zhou, Shuang Li, Yuda Wei, Yan Liu, Cheng Hu, Ben Zhou, Jun Qin, Hao Ying and Qiurong Ding ()
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Yanhao Chen: Chinese Academy of Sciences
Lanlan Chen: Chinese Academy of Sciences
Xiaoshan Wu: Chinese Academy of Sciences
Yongxu Zhao: Chinese Academy of Sciences
Yuchen Wang: Chinese Academy of Sciences
Dacheng Jiang: Chinese Academy of Sciences
Xiaojian Liu: Chinese Academy of Sciences
Tingting Zhou: Chinese Academy of Sciences
Shuang Li: Chinese Academy of Sciences
Yuda Wei: Xuzhou Medical University
Yan Liu: Chinese Academy of Sciences
Cheng Hu: Shanghai Jiao Tong University Affiliated Sixth People’s Hospital
Ben Zhou: Chinese Academy of Sciences
Jun Qin: University of Chinese Academy of Sciences, Chinese Academy of Sciences
Hao Ying: Chinese Academy of Sciences
Qiurong Ding: Chinese Academy of Sciences

Nature Communications, 2023, vol. 14, issue 1, 1-18

Abstract: Abstract The early phase lipid accumulation is essential for liver regeneration. However, whether this acute lipid accumulation can serve as signals to direct liver regeneration rather than simply providing building blocks for cell proliferation remains unclear. Through in vivo CRISPR screening, we identify MIER1 (mesoderm induction early response 1) as a key epigenetic regulator that bridges the acute lipid accumulation and cell cycle gene expression during liver regeneration in male animals. Physiologically, liver acute lipid accumulation induces the phosphorylation of EIF2S1(eukaryotic translation initiation factor 2), which consequently attenuated Mier1 translation. MIER1 downregulation in turn promotes cell cycle gene expression and regeneration through chromatin remodeling. Importantly, the lipids-EIF2S1-MIER1 pathway is impaired in animals with chronic liver steatosis; whereas MIER1 depletion significantly improves regeneration in these animals. Taken together, our studies identify an epigenetic mechanism by which the early phase lipid redistribution from adipose tissue to liver during regeneration impacts hepatocyte proliferation, and suggest a potential strategy to boost liver regeneration.

Date: 2023
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DOI: 10.1038/s41467-023-37247-9

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