ArticleNucleic acids research2010
Transcriptional corepressor SHP recruits SIRT1 histone deacetylase to inhibit LRH-1 transactivation.
Article in Nucleic acids research, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 58 citations in OpenAlex.
- Inhibition of histone deacetylase 3 alleviates lithocholic acid-induced intrahepatic cholestasis by enhancing expression of bile acid and lipid homeostasis-related genes.Acta pharmacologica Sinica · 2026Article
- Stomach at the crossroads: nuclear receptor signaling at the interface between what we are and what we eat.Physiological reviews · 2026Review
- Review
- Orphan Nuclear Receptors in Metabolic Dysfunction-associated Steatotic Liver Disease Development.Journal of clinical and translational hepatology · 2025Review
- Hepatic SIRT6 protects against cholestatic liver disease primarilyJournal of biomedical research · 2024Article
- Regulation of cholesterol homeostasis in health and diseases: from mechanisms to targeted therapeutics.Signal transduction and targeted therapy · 2022Review
- Regulation of SIRT1 and Its Roles in Inflammation.Frontiers in immunology · 2022Review
- Nuclear receptor subfamily 5 group A member 2 (NR5A2): role in health and diseases.Molecular biology reports · 2021Review
- Advances in the role of silence information regulator family in pathological pregnancy.Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences · 2021Review
- Pterostilbene Alleviates Cholestasis by Promoting SIRT1 Activity in Hepatocytes and Macrophages.Frontiers in pharmacology · 2021Article
- Xenobiotic Nuclear Receptor Signaling Determines Molecular Pathogenesis of Progressive Familial Intrahepatic Cholestasis.Endocrinology · 2018Article
- Small Heterodimer Partner Regulates Circadian Cytochromes p450 and Drug-Induced Hepatotoxicity.Theranostics · 2018Article
- Acetylation- and Methylation-Related Epigenetic Proteins in the Context of Their Targets.Genes · 2017Review
- Sirtuin 1 activation alleviates cholestatic liver injury in a cholic acid-fed mouse model of cholestasis.Hepatology (Baltimore, Md.) · 2016Article
- Orphan nuclear receptor SHP regulates iron metabolism through inhibition of BMP6-mediated hepcidin expression.Scientific reports · 2016Article
- Nuclear receptor NR5A2 controls neural stem cell fate decisions during development.Nature communications · 2016Article
- Metformin stimulates IGFBP-2 gene expression through PPARalpha in diabetic states.Scientific reports · 2016Article
- Unexpected Allosteric Network Contributes to LRH-1 Co-regulator Selectivity.The Journal of biological chemistry · 2016Article
- Sirtuins in epigenetic regulation.Chemical reviews · 2015Review
- Chenodeoxycholic Acid Reduces Hypoxia Inducible Factor-1α Protein and Its Target Genes.PloS one · 2015Article
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Orphan nuclear receptor Small Heterodimer Partner (SHP; NR0B2) is a transcriptional corepressor of a wide variety of nuclear receptors (NRs). Here, we report that SHP recruits SIRT1, a class III histone deacetylase, in an NR-specific manner to inhibit transcriptional activity. SHP interacts and co-localizes specifically with SIRT1 in vivo and inhibition of SIRT1 activity leads to a recovery from the intrinsic repressive activity of SHP but not of DAX1. Furthermore, we observed that SIRT1 does not deacetylate SHP or LRH1. However, inhibition of either SIRT1 or SHP significantly diminished the repressive effect of SHP on LRH1 transactivity. LRH1-mediated activation of CYP7A1 and SHP gene transcription was significantly repressed by both SHP and SIRT1 whereas inhibition of SIRT1 activity by inhibitors or dominant negative SIRT1 or knockdown of SHP led to a significant release of this inhibitory effect. ChIP assays revealed that SHP recruits SIRT1 on LRH1 target gene promoters and SIRT1 deacetylated template-dependent histone H3 and H4 to inhibit transcription of LRH1 target genes. Finally, we demonstrated that inhibition of SIRT1 activity significantly reversed SHP-mediated inhibition of bile-acid synthesis by LRH1 overexpression, thereby suggesting a novel mechanism of SHP-mediated inhibition of LRH1-dependent bile-acid homeostasis via recruitment of SIRT1 histone deacetylase protein.
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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.