ArticleThe Journal of biological chemistry2011
Disruption of a novel Kruppel-like transcription factor p300-regulated pathway for insulin biosynthesis revealed by studies of the c.-331 INS mutation found in neonatal diabetes mellitus.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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Who cites it
41 citing papers in PubMed, 82 citations in OpenAlex.
- Ext1 heterozygosity causes a modest effect on postprandial lipid clearance in humans.Journal of lipid research · 2015Trial
- Clinical and functional characteristics of theFrontiers in endocrinology · 2026Article
- Novel Kruppel-like factor 11 variant of maturity-onset diabetes of the young type 7: A case report.World journal of diabetes · 2025Article
- Endothelial KLF11 is a novel protector against diabetic atherosclerosis.Cardiovascular diabetology · 2024Article
- Krüpple-like factors in cardiomyopathy: emerging player and therapeutic opportunities.Frontiers in cardiovascular medicine · 2024Review
- The Role of Krüppel-like Factors in Pancreatic Physiology and Pathophysiology.International journal of molecular sciences · 2023Review
- Monogenic diabetes.Nature reviews. Disease primers · 2023Review
- Insights into the Genetics and Signaling Pathways in Maturity-Onset Diabetes of the Young.International journal of molecular sciences · 2022Review
- KLF11 Protects against Venous Thrombosis via Suppressing Tissue Factor Expression.Thrombosis and haemostasis · 2022Article
- CBP/p300 HAT maintains the gene network critical for β cell identity and functional maturity.Cell death & disease · 2021Article
- Neonatal diabetes mutations disrupt a chromatin pioneering function that activates the human insulin gene.Cell reports · 2021Article
- Monogenic diabetes: a gateway to precision medicine in diabetes.The Journal of clinical investigation · 2021Review
- Klf6 protects β-cells against insulin resistance-induced dedifferentiation.Molecular metabolism · 2020Article
- Neonatal Diabetes Mellitus.Frontiers in pediatrics · 2020Review
- KLF11 (Krüppel-Like Factor 11) Inhibits Arterial Thrombosis via Suppression of Tissue Factor in the Vascular Wall.Arteriosclerosis, thrombosis, and vascular biology · 2019Article
- The Krüppel-Like Factors and Control of Energy Homeostasis.Endocrine reviews · 2019Review
- Krüppel-like factors: Crippling and un-crippling metabolic pathways.JACC. Basic to translational science · 2018Article
- SP and KLF Transcription Factors in Digestive Physiology and Diseases.Gastroenterology · 2017Review
- Expression and functional assessment of candidate type 2 diabetes susceptibility genes identify four new genes contributing to human insulin secretion.Molecular metabolism · 2017Article
- KLF10 Mediated Epigenetic Dysregulation of Epithelial CD40/CD154 Promotes Endometriosis.Biology of reproduction · 2016Article
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Authors and funding
22 authors at 11 institutions in 3 countries.
Funding
Abstract
Krüppel-like transcription factors (KLFs) have elicited significant attention because of their regulation of essential biochemical pathways and, more recently, because of their fundamental role in the mechanisms of human diseases. Neonatal diabetes mellitus is a monogenic disorder with primary alterations in insulin secretion. We here describe a key biochemical mechanism that underlies neonatal diabetes mellitus insulin biosynthesis impairment, namely a homozygous mutation within the insulin gene (INS) promoter, c.-331C>G, which affects a novel KLF-binding site. The combination of careful expression profiling, electromobility shift assays, reporter experiments, and chromatin immunoprecipitation demonstrates that, among 16 different KLF proteins tested, KLF11 is the most reliable activator of this site. Congruently, the c.-331C>G INS mutation fails to bind KLF11, thus inhibiting activation by this transcription factor. Klf11(-/-) mice recapitulate the disruption in insulin production and blood levels observed in patients. Thus, these data demonstrate an important role for KLF11 in the regulation of INS transcription via the novel c.-331 KLF site. Lastly, our screening data raised the possibility that other members of the KLF family may also regulate this promoter under distinct, yet unidentified, cellular contexts. Collectively, this study underscores a key role for KLF proteins in biochemical mechanisms of human diseases, in particular, early infancy onset diabetes mellitus.
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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.