ArticleGene expression2016
Zinc Fingers and Homeoboxes 2 (Zhx2) Regulates Sexually Dimorphic Cyp Gene Expression in the Adult Mouse Liver.
Article in Gene expression, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 27 citations in OpenAlex.
- Host biological sex directs immune control of theFrontiers in immunology · 2026Article
- Sex Hormones and Metabolic Dysfunction-Associated Steatotic Liver Disease.International journal of molecular sciences · 2025Review
- Validation studies and multiomics analysis of Zhx2 as a candidate quantitative trait gene underlying brain oxycodone metabolite (oxymorphone) levels and behavior.The Journal of pharmacology and experimental therapeutics · 2025Article
- ScRNA-seq combined with ATAC-seq analysis to explore the metabolic balance mechanism of CCl4-induced liver inflammatory injury.Frontiers in immunology · 2025Article
- Elongation of very long chain fatty acids-3 (American journal of physiology. Gastrointestinal and liver physiology · 2023Article
- ZHX2 emerges as a negative regulator of mitochondrial oxidative phosphorylation during acute liver injury.Nature communications · 2023Article
- Cytokine storm-based mechanisms for extrapulmonary manifestations of SARS-CoV-2 infection.JCI insight · 2023Article
- Zinc fingers and homeoboxes 2 is required for diethylnitrosamine-induced liver tumor formation in C57BL/6 mice.Hepatology communications · 2022Article
- Zhx2 Is a Candidate Gene Underlying Oxymorphone Metabolite Brain Concentration Associated with State-Dependent Oxycodone Reward.The Journal of pharmacology and experimental therapeutics · 2022Article
- Sex-dependent dynamics of metabolism in primary mouse hepatocytes.Archives of toxicology · 2021Article
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- Liver size and lipid content differences between BALB/c and BALB/cJ mice on a high-fat diet are due, in part, to Zhx2.Mammalian genome : official journal of the International Mammalian Genome Society · 2019Article
- Zhx2 (zinc fingers and homeoboxes 2) regulates major urinary protein gene expression in the mouse liver.The Journal of biological chemistry · 2017Article
- Targeting H19, an Imprinted Long Non-Coding RNA, in Hepatic Functions and Liver Diseases.Diseases (Basel, Switzerland) · 2017Review
- Loss of liver-specific and sexually dimorphic gene expression by aryl hydrocarbon receptor activation in C57BL/6 mice.PloS one · 2017Article
- Article
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
The mammalian cytochrome P450 (Cyp) gene family encodes a large number of structurally related enzymes that catalyze a variety of metabolic and detoxification reactions. The liver is the primary site of Cyp expression in terms of expression levels and number of expressed genes, consistent with this organ's essential role in metabolism of endogenous and xenobiotic compounds. Many Cyp genes exhibit sexually dimorphic expression. For example, Cyp2a4 is expressed significantly higher in the adult liver of female mice compared to male mice. An exception to this pattern is seen in BALB/cJ mice, where male hepatic Cyp2a4 mRNA levels are substantially elevated compared to male mice of other strains. The Zinc fingers and homeoboxes 2 (Zhx2) protein governs the silencing of several genes in the postnatal liver, including α-fetoprotein, H19, and glypican 3. Zhx2 also regulates numerous hepatic genes that govern lipid homeostasis. We previously showed that the Zhx2 gene is mutated in BALB/cJ mice, which led us to consider whether elevated male hepatic Cyp2a4 levels in this strain are due to this Zhx2 mutation. Using mice with a conditional Zhx2 deletion, we show here that the absence of Zhx2 in hepatocytes results in increased Cyp2a4 expression in adult male liver. We extend this finding to show that additional Cyp genes are disregulated in the absence of Zhx2. We also show that mRNA levels of Cyp2a4 and several other female-biased Cyp genes are increased, and male-biased Cyp4a12 is decreased in mouse liver tumors. These data indicate that Zhx2 is a novel regulator of sex-biased Cyp gene expression in the normal and diseased liver.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.