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Multicellular organisms contain a variety of structurally and functionally distinct cell types, but the DNA in all the cells originated from the same parent cells. The differences in the cells can be attributed to the differential gene expression. Liver cells, whose functions include detoxification of blood, production of bile to metabolize fats, and synthesis of proteins essential for metabolism, must express a specific set of genes to perform their functions. Gene expression also varies with...
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Rapidly dividing tumors, embryos, and wounded tissues require more oxygen than usual, lowering the oxygen concentration in the blood. At low oxygen or hypoxic conditions, an oxygen-sensitive transcription factor called the hypoxia-inducible factor 1 or HIF1 is activated. HIF1 is a dimeric protein of alpha (ɑ) and beta (β) subunits.  Under optimal oxygen conditions, HIF1β is present in the nucleus while HIF1ɑ remains in the cytosol. HIF1ɑ is hydroxylated by prolyl...
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Nuclear receptors, or NRs, are unique transcription factors that regulate gene transcription and affect the cellular pathways involved in reproduction, development, or metabolism. Their ability to be stimulated by small lipophilic ligands and control vital cellular processes makes them ideal drug targets. Nearly 10-15% of currently prescribed drugs target these receptors.
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Cell Type-specific Gene Expression Profiling in the Mouse Liver
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Regulation of Hepatic Xenosensor Function by HNF4alpha.

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    Hepatocyte nuclear factor 4alpha (HNF4α) is crucial for the function of key xenobiotic sensors Constitutive Androstane Receptor (CAR), Pregnane X Receptor (PXR), and Peroxisome Proliferator-Activated Receptor-alpha (PPARα), impacting toxicological responses.

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    Area of Science:

    • Hepatology
    • Molecular Toxicology
    • Nuclear Receptor Signaling

    Background:

    • Nuclear receptors like Aryl hydrocarbon Receptor (AhR), Constitutive Androstane Receptor (CAR), Pregnane X Receptor (PXR), and Peroxisome Proliferator-Activated Receptor-alpha (PPARα) are vital xenobiotic sensors.
    • Hepatocyte nuclear factor 4alpha (HNF4α) is an essential orphan nuclear receptor for liver function.

    Conclusions:

    • HNF4α is critical for the functional activation of hepatic CAR, PXR, and PPARα.
    • HNF4α is not essential for AhR activation.
    • These findings highlight HNF4α's indispensable role in mediating hepatic xenobiotic sensor function and subsequent toxicological responses.