ArticleCell death & disease2018
The type 2 diabetes-associated HMG20A gene is mandatory for islet beta cell functional maturity.
Article in Cell death & disease, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers, 1 of them a synthesis that pooled it.
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Who cites it
31 citing papers in PubMed, 1 synthesis or guideline pooled it, 45 citations in OpenAlex.
- The landscape of GWAS validation; systematic review identifying 309 validated non-coding variants across 130 human diseases.BMC medical genomics · 2022Pooled it
- Experimental models in diabetes research.Laboratory animal research · 2026Review
- Single-cell-marker-based subtyping and multi-level analyses uncover the prognostic effects, dysregulations and therapeutic indicative potential of an eight-gene signature in lung adenocarcinoma.Cancer cell international · 2026Article
- Signal transduction pathways controllingiScience · 2025Article
- LRH-1/NR5A2 targets mitochondrial dynamics to reprogram type 1 diabetes macrophages and dendritic cells into an immune tolerance phenotype.Clinical and translational medicine · 2024Article
- TIPRL Regulates Stemness and Survival in Lung Cancer Stem Cells through CaMKK2-CaMK4-CREB Feedback Loop Activation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Article
- The role of neurovascular coupling dysfunction in cognitive decline of diabetes patients.Frontiers in neuroscience · 2024Review
- Identification and validation of core genes for type 2 diabetes mellitus by integrated analysis of single-cell and bulk RNA-sequencing.European journal of medical research · 2023Article
- Diabetes mellitus type 2 as an underlying, comorbid or consequent state of mental disorders.World journal of diabetes · 2023Review
- Article
- Genetic Variants Associated with Poor Responsiveness to Sulfonylureas in Filipinos with Type 2 Diabetes Mellitus.Journal of the ASEAN Federation of Endocrine Societies · 2023Article
- HMG20A was identified as a key enhancer driver associated with DNA damage repair in oral squamous cell carcinomas.BMC oral health · 2022Article
- The high mobility group protein HMG20A cooperates with the histone reader PHF14 to modulate TGFβ and Hippo pathways.Nucleic acids research · 2022Article
- HMG20A Inhibit Adipogenesis by Transcriptional and Epigenetic Regulation of MEF2C Expression.International journal of molecular sciences · 2022Article
- NR5A2/LRH-1 regulates the PTGS2-PGEiScience · 2022Article
- Genome-wide association study reveals candidate genes relevant to body weight in female turkeys (Meleagris gallopavo).PloS one · 2022Article
- The Human Islet: Mini-Organ With Mega-Impact.Endocrine reviews · 2021Review
- Harnessing the Endogenous Plasticity of Pancreatic Islets: A Feasible Regenerative Medicine Therapy for Diabetes?International journal of molecular sciences · 2021Review
- The Plasticity of Pancreatic β-Cells.Metabolites · 2021Review
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Authors and funding
22 authors at 6 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
HMG20A (also known as iBRAF) is a chromatin factor involved in neuronal differentiation and maturation. Recently small nucleotide polymorphisms (SNPs) in the HMG20A gene have been linked to type 2 diabetes mellitus (T2DM) yet neither expression nor function of this T2DM candidate gene in islets is known. Herein we demonstrate that HMG20A is expressed in both human and mouse islets and that levels are decreased in islets of T2DM donors as compared to islets from non-diabetic donors. In vitro studies in mouse and human islets demonstrated that glucose transiently increased HMG20A transcript levels, a result also observed in islets of gestating mice. In contrast, HMG20A expression was not altered in islets from diet-induced obese and pre-diabetic mice. The T2DM-associated rs7119 SNP, located in the 3' UTR of the HMG20A transcript reduced the luciferase activity of a reporter construct in the human beta 1.1E7 cell line. Depletion of Hmg20a in the rat INS-1E cell line resulted in decreased expression levels of its neuronal target gene NeuroD whereas Rest and Pax4 were increased. Chromatin immunoprecipitation confirmed the interaction of HMG20A with the Pax4 gene promoter. Expression levels of Mafa, Glucokinase, and Insulin were also inhibited. Furthermore, glucose-induced insulin secretion was blunted in HMG20A-depleted islets. In summary, our data demonstrate that HMG20A expression in islet is essential for metabolism-insulin secretion coupling via the coordinated regulation of key islet-enriched genes such as NeuroD and Mafa and that depletion induces expression of genes such as Pax4 and Rest implicated in beta cell de-differentiation. More importantly we assign to the T2DM-linked rs7119 SNP the functional consequence of reducing HMG20A expression likely translating to impaired beta cell mature function.
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