ArticleThe Journal of biological chemistry2010
Distinct regulation of hepatic nuclear factor 1alpha by NKX6.1 in pancreatic beta cells.
Article in The Journal of biological chemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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Who cites it
7 citing papers in PubMed, 12 citations in OpenAlex.
- MODY Only Monogenic? A Narrative Review of theInternational journal of molecular sciences · 2024Review
- Deficiency of transcription factor Nkx6.1 does not prevent insulin secretion in INS-1E cells.Scientific reports · 2023Article
- HNF1A：From Monogenic Diabetes to Type 2 Diabetes and Gestational Diabetes Mellitus.Frontiers in endocrinology · 2022Review
- NKX6.1 transcription factor: a crucial regulator of pancreatic β cell development, identity, and proliferation.Stem cell research & therapy · 2020Review
- NKX6.1 functions as a metastatic suppressor through epigenetic regulation of the epithelial-mesenchymal transition.Oncogene · 2016Article
- Pancreatic and duodenal homeobox gene 1 (Pdx1) down-regulates hepatic transcription factor 1 alpha (HNF1α) expression during reprogramming of human hepatic cells into insulin-producing cells.American journal of translational research · 2015Article
- Prioritization of biomarker targets in human umbilical cord blood: identification of proteins in infant blood serving as validated biomarkers in adults.Environmental health perspectives · 2012Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
Hepatic nuclear factor 1alpha (HNF1alpha) is a key regulator of development and function in pancreatic beta cells and is specifically involved in regulation of glycolysis and glucose-stimulated insulin secretion. Abnormal expression of HNF1alpha leads to development of MODY3 (maturity-onset diabetes of the young 3). We report that NK6 homeodomain 1 (NKX6.1) binds to a cis-regulatory element in the HNF1alpha promoter and is a major regulator of this gene in beta cells. We identified an NKX6.1 recognition sequence in the distal region of the HNF1alpha promoter and demonstrated specific binding of NKX6.1 in beta cells by electrophoretic mobility shift and chromatin immunoprecipitation assays. Site-directed mutagenesis of the NKX6.1 core-binding sequence eliminated NKX6.1-mediated activation and substantially decreased activity of the HNF1alpha promoter in beta cells. Overexpression or small interfering RNA-mediated knockdown of the Nkx6.1 gene resulted in increased or diminished HNF1alpha gene expression, respectively, in beta cells. We conclude that NKX6.1 is a novel regulator of HNF1alpha in pancreatic beta cells. This novel regulatory mechanism for HNF1alpha in beta cells may provide new molecular targets for the diagnosis of MODY3.
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Registered trials
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.