ArticleThe Journal of biological chemistry2009
MODY7 gene, KLF11, is a novel p300-dependent regulator of Pdx-1 (MODY4) transcription in pancreatic islet beta cells.
Article in The Journal of biological chemistry, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 63 papers.
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Who cites it
63 citing papers in PubMed, 106 citations in OpenAlex.
- The Genetic Landscape of Diabetes Mellitus: Lessons from Monogenic and Polygenic Forms.Life (Basel, Switzerland) · 2026Review
- Review
- Review
- Decoding MODY: exploring genetic roots and clinical pathways.Diabetology international · 2025Review
- Endothelial KLF11 is a novel protector against diabetic atherosclerosis.Cardiovascular diabetology · 2024Article
- Modelling human diabetesFrontiers in endocrinology · 2024Review
- A critical review on therapeutic approaches of CRISPR-Cas9 in diabetes mellitus.Naunyn-Schmiedeberg's archives of pharmacology · 2023Review
- KLF4 regulates skeletal muscle development and regeneration by directly targeting P57 and Myomixer.Cell death & disease · 2023Article
- KLF11 is an independent negative prognostic factor for breast cancer from a cohort study and induces proliferation and inhibits apoptosis in vitro.Breast cancer (Tokyo, Japan) · 2023Article
- Demethylase-independent roles of LSD1 in regulating enhancers and cell fate transition.Nature communications · 2023Article
- The Role of Krüppel-like Factors in Pancreatic Physiology and Pathophysiology.International journal of molecular sciences · 2023Review
- Novel gene mutation in maturity-onset diabetes of the young: A case report.World journal of clinical cases · 2023Article
- Statistical evidence for high-penetrance MODY-causing genes in a large population-based cohort.Endocrinology, diabetes & metabolism · 2022Article
- Insights into the Genetics and Signaling Pathways in Maturity-Onset Diabetes of the Young.International journal of molecular sciences · 2022Review
- Maturity-Onset Diabetes of the Young: Mutations, Physiological Consequences, and Treatment Options.Journal of personalized medicine · 2022Review
- Aging compromises human islet beta cell function and identity by decreasing transcription factor activity and inducing ER stress.Science advances · 2022Article
- KLF11 Protects against Venous Thrombosis via Suppressing Tissue Factor Expression.Thrombosis and haemostasis · 2022Article
- Regulation of Pdx1 by oxidative stress and Nrf2 in pancreatic beta-cells.Frontiers in endocrinology · 2022Review
- β-Arrestin-1 is required for adaptive β-cell mass expansion during obesity.Nature communications · 2021Article
- CBP/p300 HAT maintains the gene network critical for β cell identity and functional maturity.Cell death & disease · 2021Article
3 more citing papers are in PubMed but not listed here.
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Authors and funding
7 authors at 4 institutions in 3 countries.
Funding
Abstract
Pdx-1 (pancreatic-duodenal homeobox-1), a MODY4 homeodomain transcription factor, serves as a master regulator in the pancreas because of its importance during organogenesis and in adult islet insulin-producing beta cell activity. Here, we show that KLF11, an SP/Krüppel-like (SP/KLF) transcription factor, mutated in French maturity onset diabetes of the young patients (MODY7), regulates Pdx-1 transcription in beta cells through two evolutionarily conserved GC-rich motifs in conserved Area II, a control region essential to islet beta cell-enriched expression. These regulatory elements, termed GC1 (human base pair -2061/-2055) and GC2 (-2036/-2027), are also nearly identical to the consensus KLF11 binding sequence defined here by random oligonucleotide binding analysis. KLF11 specifically associates with Area II in chromatin immunoprecipitation assays, while preventing binding to GC1- and/or GC2-compromised Pdx1-driven reporter activity in beta cell lines. Mechanistically, we find that KLF11 interacts with the coactivator p300 via its zinc finger domain in vivo to mediate Pdx-1 activation. Together, our data identified a hierarchical regulatory cascade for these two MODY genes, suggesting that gene regulation in MODY is more complex than anticipated previously. Furthermore, because KLF11 like most MODY-associated transcription factors uses p300, these data further support a role for this coactivator as a critical chromatin link in forms of type 2 diabetes.
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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.