ArticleThe Journal of biological chemistry2015
Transcriptional activity of the islet β cell factor Pdx1 is augmented by lysine methylation catalyzed by the methyltransferase Set7/9.
Article in The Journal of biological chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers, 1 of them a synthesis that pooled it.
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Who cites it
27 citing papers in PubMed, 1 synthesis or guideline pooled it, 45 citations in OpenAlex.
- Roles of Epigenetic Modifications in the Differentiation and Function of Pancreatic β-Cells.Frontiers in cell and developmental biology · 2020Pooled it
- Emerging Roles of Post-Translational Modifications in Metabolic Homeostasis and Type 2 Diabetes.International journal of molecular sciences · 2025Review
- Lysine and arginine methylation of transcription factors.Cellular and molecular life sciences : CMLS · 2024Review
- Histone Methylation, Energy Metabolism, and Alzheimer's Disease.Aging and disease · 2024Review
- Roles of Lysine Methylation in Glucose and Lipid Metabolism: Functions, Regulatory Mechanisms, and Therapeutic Implications.Biomolecules · 2024Review
- Lysine-specific methyltransferase Set7/9 in stemness, differentiation, and development.Biology direct · 2024Review
- Set7/9 aggravates ischemic brain injury via enhancing glutamine metabolism in a blocking Sirt5 manner.Cell death and differentiation · 2024Article
- Metabolo-epigenetic interplay provides targeted nutritional interventions in chronic diseases and ageing.Frontiers in oncology · 2023Review
- Methyltransferase Set7/9 as a Multifaceted Regulator of ROS Response.International journal of biological sciences · 2023Review
- Article
- The Ldb1 transcriptional co-regulator is required for establishment and maintenance of the pancreatic endocrine lineage.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2022Article
- PDX1 is the cornerstone of pancreatic β-cell functions and identity.Frontiers in molecular biosciences · 2022Review
- Probing multiple enzymatic methylation events in real time with NMR spectroscopy.Biophysical journal · 2021Article
- SetD7 (Set7/9) is a novel target of PPARγ that promotes the adaptive pancreatic β-cell glycemic response.The Journal of biological chemistry · 2021Article
- Epigenetic Regulation of PDX-1 in Type 2 Diabetes Mellitus.Diabetes, metabolic syndrome and obesity : targets and therapy · 2021Review
- Epigenetic Regulation of β Cell Identity and Dysfunction.Frontiers in endocrinology · 2021Review
- Epigenetics in β-cell adaptation and type 2 diabetes.Current opinion in pharmacology · 2020Review
- The Lysine Demethylase KDM5B Regulates Islet Function and Glucose Homeostasis.Journal of diabetes research · 2019Article
- SETD7 in cardiomyocyte differentiation and cardiac function.Stem cell investigation · 2019Article
- Identification of Rpl29 as a major substrate of the lysine methyltransferase Set7/9.The Journal of biological chemistry · 2018Article
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 1 country.
Funding
Abstract
The transcription factor Pdx1 is crucial to islet β cell function and regulates target genes in part through interaction with coregulatory factors. Set7/9 is a Lys methyltransferase that interacts with Pdx1. Here we tested the hypothesis that Lys methylation of Pdx1 by Set7/9 augments Pdx1 transcriptional activity. Using mass spectrometry and mutational analysis of purified proteins, we found that Set7/9 methylates the N-terminal residues Lys-123 and Lys-131 of Pdx1. Methylation of these residues occurred only in the context of intact, full-length Pdx1, suggesting a specific requirement of secondary and/or tertiary structural elements for catalysis by Set7/9. Immunoprecipitation assays and mass spectrometric analysis using β cells verified Lys methylation of endogenous Pdx1. Cell-based luciferase reporter assays using wild-type and mutant transgenes revealed a requirement of Pdx1 residue Lys-131, but not Lys-123, for transcriptional augmentation by Set7/9. Lys-131 was not required for high-affinity interactions with DNA in vitro, suggesting that its methylation likely enhances post-DNA binding events. To define the role of Set7/9 in β cell function, we generated mutant mice in which the gene encoding Set7/9 was conditionally deleted in β cells (Set(Δ)β). Set(Δ)β mice exhibited glucose intolerance similar to Pdx1-deficient mice, and their isolated islets showed impaired glucose-stimulated insulin secretion with reductions in expression of Pdx1 target genes. Our results suggest a previously unappreciated role for Set7/9-mediated methylation in the maintenance of Pdx1 activity and β cell function.
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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.