ArticleMolecular and cellular biology2006
Threshold levels of hepatocyte nuclear factor 6 (HNF-6) acting in synergy with HNF-4 and PGC-1alpha are required for time-specific gene expression during liver development.
Article in Molecular and cellular biology, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 60 citations in OpenAlex.
- Bridging pancreatic and hepatic development: overlapping genes and their role in diabetes.Cellular & molecular biology letters · 2025Review
- Integrative pan-cancer analysis reveals a common architecture of dysregulated transcriptional networks characterized by loss of enhancer methylation.PLoS computational biology · 2024Article
- New advances of NG2-expressing cell subset in marrow mesenchymal stem cells as novel therapeutic tools for liver fibrosis/cirrhosis.Stem cell research & therapy · 2024Article
- Functional characterization of HNF4A gene variants identify promoter and cell line specific transactivation effects.Human molecular genetics · 2024Article
- Peroxisome proliferator-activated receptor gamma coactivator-1 (PGC-1) family in physiological and pathophysiological process and diseases.Signal transduction and targeted therapy · 2024Review
- [Culture of pluripotent stem cell-derived hepatocytes and organoids].Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology · 2022Article
- Unraveling the molecular mechanisms of hyperlipidemia using integrated lncRNA and mRNA microarray data.Experimental and therapeutic medicine · 2022Article
- Transcription Control of Liver Development.Cells · 2021Review
- Interconnections between circadian clocks and metabolism.The Journal of clinical investigation · 2021Review
- Review
- Onecut Factors and Pou2f2 Regulate the Distribution of V2 Interneurons in the Mouse Developing Spinal Cord.Frontiers in cellular neuroscience · 2019Article
- Review
- HNF6 and Rev-erbα integrate hepatic lipid metabolism by overlapping and distinct transcriptional mechanisms.Genes & development · 2016Article
- Developmental Stage-Specific Embryonic Induction of HepG2 Cell Differentiation.Digestive diseases and sciences · 2016Article
- Cross Talk Between GH-Regulated Transcription Factors HNF6 and CUX2 in Adult Mouse Liver.Molecular endocrinology (Baltimore, Md.) · 2015Article
- Developmental Stage-Specific Hepatocytes Induce Maturation of HepG2 Cells by Rebuilding the Regulatory Circuit.Molecular medicine (Cambridge, Mass.) · 2015Article
- Differentiation of progenitors in the liver: a matter of local choice.The Journal of clinical investigation · 2013Review
- Neurogenin 3+ cells contribute to β-cell neogenesis and proliferation in injured adult mouse pancreas.Cell death & disease · 2013Article
- Onecut transcription factors act upstream of Isl1 to regulate spinal motoneuron diversification.Development (Cambridge, England) · 2012Article
- Correlation analysis between gene expression profile of rat liver tissues and high-fat emulsion-induced nonalcoholic fatty liver.Digestive diseases and sciences · 2011Article
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
During liver development, hepatocytes undergo a maturation process that leads to the fully differentiated state. This relies at least in part on the coordinated action of liver-enriched transcription factors (LETFs), but little is known about the dynamics of this coordination. In this context we investigate here the role of the LETF hepatocyte nuclear factor 6 (HNF-6; also called Onecut-1) during hepatocyte differentiation. We show that HNF-6 knockout mouse fetuses have delayed expression of glucose-6-phosphatase (g6pc), which catalyzes the final step of gluconeogenesis and is a late marker of hepatocyte maturation. Using a combination of in vivo and in vitro gain- and loss-of-function approaches, we demonstrate that HNF-6 stimulates endogenous g6pc gene expression directly via a synergistic and interdependent action with HNF-4 and that it involves coordinate recruitment of the coactivator PGC-1alpha. The expression of HNF-6, HNF-4, and PGC-1alpha rises steadily during liver development and precedes that of g6pc. We provide evidence that threshold levels of HNF-6 are required to allow synergism between HNF-6, HNF-4, and PGC-1alpha to induce time-specific expression of g6pc. Our observations on the regulation of g6pc by HNF-6 provide a model whereby synergism, interdependency, and threshold concentrations of LETFs and coactivators determine time-specific expression of genes during liver development.
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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.