We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Acute liver steatosis translationally controls the epigenetic regulator MIER1 to promote liver regeneration in a study with male mice.
- Authors
Chen, Yanhao; Chen, Lanlan; Wu, Xiaoshan; Zhao, Yongxu; Wang, Yuchen; Jiang, Dacheng; Liu, Xiaojian; Zhou, Tingting; Li, Shuang; Wei, Yuda; Liu, Yan; Hu, Cheng; Zhou, Ben; Qin, Jun; Ying, Hao; Ding, Qiurong
- 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. Early lipid accumulation is thought to contribute to liver regeneration through unclear functional mechanisms. Here the authors identify an epigenetic regulator, MIER1, that bridges the acute lipid accumulation and cell cycle gene transcription during liver regeneration after surgical resection in male mice.
- Subjects
LIVER regeneration; LIVER cells; FATTY degeneration; EPIGENETICS; LIVER; CELL cycle; GENE expression
- Publication
Nature Communications, 2023, Vol 14, Issue 1, p1
- ISSN
2041-1723
- Publication type
Article
- DOI
10.1038/s41467-023-37247-9