ArticleMolecular and cellular biology2008
Hepatocyte nuclear factor 4alpha contributes to thyroid hormone homeostasis by cooperatively regulating the type 1 iodothyronine deiodinase gene with GATA4 and Kruppel-like transcription factor 9.
Article in Molecular and cellular biology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers, 1 of them a synthesis that pooled it.
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Who cites it
22 citing papers in PubMed, 1 synthesis or guideline pooled it, 42 citations in OpenAlex.
- The associations between immunity-related genes and breast cancer prognosis in Korean women.PloS one · 2014Pooled it
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- PFAS Environmental Pollution and Antioxidant Responses: An Overview of the Impact on Human Field.International journal of environmental research and public health · 2020Review
- Novel Transcriptional Mechanisms for Regulating Metabolism by Thyroid Hormone.International journal of molecular sciences · 2018Review
- Plasma Concentrations of Perfluoroalkyl Substances and Risk of Type 2 Diabetes: A Prospective Investigation among U.S. Women.Environmental health perspectives · 2018Article
- A pre-neoplastic epigenetic field defect in HCV-infected liver at transcription factor binding sites and polycomb targets.Oncogene · 2017Article
- GATA4 promotes hepatoblastoma cell proliferation by altering expression of miR125b and DKK3.Oncotarget · 2016Article
- Crosstalk of HNF4Acta pharmaceutica Sinica. B · 2016Review
- Aberrant Cerebellar Development in Mice Lacking Dual Oxidase Maturation Factors.Thyroid : official journal of the American Thyroid Association · 2016Article
- Desensitization and Incomplete Recovery of Hepatic Target Genes After Chronic Thyroid Hormone Treatment and Withdrawal in Male Adult Mice.Endocrinology · 2016Article
- The KDM3A-KLF2-IRF4 axis maintains myeloma cell survival.Nature communications · 2016Article
- The FBXL10/KDM2B scaffolding protein associates with novel polycomb repressive complex-1 to regulate adipogenesis.The Journal of biological chemistry · 2015Article
- A thyroid hormone receptor/KLF9 axis in human hepatocytes and pluripotent stem cells.Stem cells (Dayton, Ohio) · 2015Article
- Krüppel-like factor 9 promotes hepatic cytochrome P450 2D6 expression during pregnancy in CYP2D6-humanized mice.Molecular pharmacology · 2014Article
- Krüppel-like factors are effectors of nuclear receptor signaling.General and comparative endocrinology · 2014Review
- Transdifferentiation of human fibroblasts into hepatocyte-like cells by defined transcriptional factors.Hepatology international · 2013Article
- Cold-induced changes in gene expression in brown adipose tissue, white adipose tissue and liver.PloS one · 2013Article
- A genome-wide screen indicates correlation between differentiation and expression of metabolism related genes.PloS one · 2013Article
- The thyrotropin-releasing hormone gene is regulated by thyroid hormone at the level of transcription in vivo.Endocrinology · 2010Article
Corrections and comments
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Authors and funding
16 authors at 4 institutions in 2 countries.
Funding
Abstract
Type 1 iodothyronine deiodinase (Dio1), a selenoenzyme catalyzing the bioactivation of thyroid hormone, is highly expressed in the liver. Dio1 mRNA and enzyme activity levels are markedly reduced in the livers of hepatocyte nuclear factor 4alpha (HNF4alpha)-null mice, thus accounting for its liver-specific expression. Consistent with this deficiency, serum T4 and rT3 concentrations are elevated in these mice compared with those in HNF4alpha-floxed control littermates; however, serum T3 levels are unchanged. Promoter analysis of the mouse Dio1 gene demonstrated that HNF4alpha plays a key role in the transactivation of the mouse Dio1 gene. Deletion and substitution mutation analyses demonstrated that a proximal HNF4alpha site (direct repeat 1 [TGGACAAAGGTGC]; HNF4alpha-RE) is crucial for transactivation of the mouse Dio1 gene by HNF4alpha. Mouse Dio1 is also stimulated by thyroid hormone signaling, but a direct role for thyroid hormone receptor action has not been reported. We also showed that thyroid hormone-inducible Krüppel-like factor 9 (KLF9) stimulates the mouse Dio1 promoter very efficiently through two CACCC sequences that are located on either side of HNF4alpha-RE. Furthermore, KLF9 functions together with HNF4alpha and GATA4 to synergistically activate the mouse Dio1 promoter, suggesting that Dio1 is regulated by thyroid hormone in the mouse through an indirect mechanism requiring prior KLF9 induction. In addition, we showed that physical interactions between the C-terminal zinc finger domain (Cf) of GATA4 and activation function 2 of HNF4alpha and between the basic domain adjacent to Cf of GATA4 and a C-terminal domain of KLF9 are both required for this synergistic response. Taken together, these results suggest that HNF4alpha regulates thyroid hormone homeostasis through transcriptional regulation of the mouse Dio1 gene with GATA4 and KLF9.
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