ArticleHepatology (Baltimore, Md.)2012
Liver-specific ablation of Krüppel-associated box-associated protein 1 in mice leads to male-predominant hepatosteatosis and development of liver adenoma.
Article in Hepatology (Baltimore, Md.), 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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38 citing papers in PubMed, 57 citations in OpenAlex.
- Ancestry informative genetic variants associated with tobacco metabolic and detoxification capacity measured by 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) among smokers.Archives of toxicology · 2026Article
- SRSF3-TRIM28-MDC1 prevents DNA damage caused by R-loops in fatty liver disease in mice.JCI insight · 2026Article
- KAP1 in antiviral immunity: dual roles in viral silencing and immune regulation.Frontiers in cellular and infection microbiology · 2025Review
- KAP1 stabilizes MYCN mRNA and promotes neuroblastoma tumorigenicity by protecting the RNA mJournal of experimental & clinical cancer research : CR · 2024Article
- TRIM28 in cancer and cancer therapy.Frontiers in genetics · 2024Review
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- The role of TRIM family in metabolic associated fatty liver disease.Frontiers in endocrinology · 2023Review
- TRIM proteins in hepatocellular carcinoma.Journal of biomedical science · 2022Review
- Enhanced Expression of Human Endogenous Retroviruses, TRIM28 and SETDB1 in Autism Spectrum Disorder.International journal of molecular sciences · 2022Article
- Sex differences in the intergenerational inheritance of metabolic traits.Nature metabolism · 2022Review
- Regulation of p53 by E3s.Cancers · 2021Review
- Deletion of Trim28 in committed adipocytes promotes obesity but preserves glucose tolerance.Nature communications · 2021Article
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- KAP1 targets actively transcribed genomic loci to exert pleomorphic effects on RNA polymerase II activity.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2020Article
- Article
- Hdac3, Setdb1, and Kap1 mark H3K9me3/H3K14ac bivalent regions in young and aged liver.Aging cell · 2020Article
- Downregulation of TRIM28 inhibits growth and increases apoptosis of nude mice with non‑small cell lung cancer xenografts.Molecular medicine reports · 2018Article
- The complexity of TRIM28 contribution to cancer.Journal of biomedical science · 2017Review
- KRAB zinc finger proteins.Development (Cambridge, England) · 2017Review
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Authors and funding
12 authors at 3 institutions in 1 country.
Funding
Abstract
unlabelledThe liver is characterized by sexually dimorphic gene expression translating into sex-specific differences in lipid, drug, steroid hormone, and xenobiotic metabolism, with distinct responses of males and females to environmental challenges. Here, we investigated the role of the Krüppel-associated box (KRAB)-associated protein 1 (KAP1) epigenetic regulator in this process. Liver-specific KAP1 knockout (KO) led to strikingly sexually dimorphic phenotypic disturbances, including male-predominant steatosis and hepatic tumors with up-regulation of protein kinase B and extracellular signal-related kinases 1/2 mitogen-activated protein kinase signaling. This correlated with the sex-specific transcriptional dysregulation of a wide range of metabolic genes, notably those involved in retinol and sex hormone processing as well as in detoxification. Furthermore, chromatin immunoprecipitation followed by deep sequencing indicated that a number of dysregulated genes are direct targets of the KRAB/KAP1 repression system. Those genes include sexually dimorphic cytochrome P 450 Cyp2d9, glutathione S-transferase π, Cyp2a, Cyp2b, and Cyp3a gene clusters. Additionally, we identified a male-restricted KAP1-binding site in the fat-specific protein 27 gene, correlating with its male-predominant up-regulation upon Kap1 deletion, suggesting that the latter might be an important trigger in the development of male-specific hepatosteatosis and secondary tumorigenesis.
conclusionThis work reveals KRAB/KAP1-mediated transcriptional regulation as a central event in metabolic control hormones, drugs, and xenobiotics in the liver and further links disturbances in these processes with hepatic carcinogenesis.
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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.