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Updated: Feb 23, 2026

Cell Type-specific Gene Expression Profiling in the Mouse Liver
Published on: September 17, 2019
Transcriptional and post-transcriptional activation of GATA4 contributes to liver regeneration
Xiulian Miao1, Wenhui Dong2, Jiawen Zhou3
1Institute of Biomedical Research, College of Agriculture and Life Science, Liaocheng University, Liaocheng, China.
Aims:
Hepatocytes can resume proliferation to replenish the loss of liver mass following liver injury in a process known as liver regeneration. In the present study we investigated the role of GATA4, a zinc finger-containing transcription factor, in this process.
Methods And Materials:
Liver regeneration was modeled in vitro by treating primary hepatocytes with hepatocytes growth factor (HGF). Liver regeneration was modeled in mice subjected to partial hepatectomy (PHx) or acetaminophen (APAP) injection.
Key Findings:
We report that GATA4 expression was up-regulated in hepatocytes at both transcriptional and post-translational levels during liver regeneration. c-Jun bound to the Gata4 promoter and activated Gata4 transcription. In addition, the ubiquitin E3 ligase Cullin 4a (Cul4a) interacted with GATA4 to promote its degradation; down-regulation of Cul4a enabled GATA4 stabilization and accumulation. GATA4 knockdown attenuated HGF-induced proliferation of hepatocytes in vitro and weakened liver regeneration following PHx or APAP injection in mice. Importantly, GATA4 expression was detected to be positively correlated with proliferation of hepatocytes and inversely correlated with liver injury in patients with acute liver failure.
Significance:
Our data unveil a novel role of GATA4 in liver regeneration and its implication in acute liver failure.
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