Transcriptional control in the mammalian liver: liver development, perinatal repression, and zonal gene regulation
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- Spear, B.T., Jin, L., Ramasamy, S. et al. Cell. Mol. Life Sci. (2006) 63: 2922. doi:10.1007/s00018-006-6258-5
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Liver function is crucial for maintaining metabolic homeostasis in mammals. Numerous genes must be properly regulated for the liver to develop and perform a variety of activities. Several recent gene-knockout studies in mice have clarified the roles of GATA6, HNF4α, and Foxa1/Foxa2 in early stages of liver formation. After the liver forms, transcriptional changes continue to occur; during the perinatal period, certain genes such as α-fetoprotein and H19 are silenced, others are activated, and position-dependent (or zonal) regulation is established. Zhx2 was recently identified as one factor involved in postnatal repression of α-fetoprotein and other genes. Furthermore, several studies indicate that negative regulation is involved in the zonal control of glutamine synthetase. Finally, exciting new evidence indicates that signaling through the Wnt/β-catenin pathway is also involved in zonal regulation in the adult liver.