ArticleGenes & development2011
Nkx2.2 repressor complex regulates islet β-cell specification and prevents β-to-α-cell reprogramming.
Article in Genes & development, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 131 papers, 1 of them a synthesis that pooled it.
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Who cites it
131 citing papers in PubMed, 1 synthesis or guideline pooled it, 202 citations in OpenAlex.
- Roles of Epigenetic Modifications in the Differentiation and Function of Pancreatic β-Cells.Frontiers in cell and developmental biology · 2020Pooled it
- Mechanisms underlying disease-causing variants in promoters and enhancers.Nature genetics · 2026Review
- Developmental Control of DNA Damage Responses in α- and β-Cells Shapes the Selective β-Cell Susceptibility in Diabetes.Diabetes · 2026Article
- Understanding development and cellular plasticity in the pancreas in health and disease.Nature reviews. Gastroenterology & hepatology · 2026Review
- CHD4 and NKX2.2 Cooperate to Regulate β-Cell Function by Repressing Non-β-Cell Gene Programs.Diabetes · 2026Article
- Independent control of neurogenesis and dorsoventral patterning by NKX2-2.Genes & development · 2026Article
- Article
- Cells Co-Producing Insulin and Glucagon in Congenital Hyperinsulinism.Life (Basel, Switzerland) · 2025Article
- Obesity and Its Role in Fetal Programming-A Narrative Review.Nutrients · 2025Review
- Developmental control of DNA damage responses in α- and β-cells shapes the selective beta-cell susceptibility in diabetes.bioRxiv : the preprint server for biology · 2025Article
- CHD4 and NKX2.2 Cooperate to Regulate Beta Cell Function by Repressing Non-Beta Cell Gene Programs.bioRxiv : the preprint server for biology · 2025Article
- Human NKX2.2 influences islet endocrine cell fate choices through regulation of WNT pathway genes.bioRxiv : the preprint server for biology · 2025Article
- NKX2.2 and KLF4 cooperate to regulate α-cell identity.Genes & development · 2025Article
- Post translational modification regulation of transcription factors governing pancreatic β-cell identity and functional mass.Frontiers in endocrinology · 2025Review
- Nzf2 promotes oligodendrocyte differentiation and regeneration via repressing HDAC1-mediated histone deacetylation.Science advances · 2024Article
- Targeting β-Cell Plasticity: A Promising Approach for Diabetes Treatment.Current issues in molecular biology · 2024Review
- Glucose metabolism partially regulates β-cell function through epigenomic changes.Journal of diabetes investigation · 2024Review
- Canalizing cell fate by transcriptional repression.Molecular systems biology · 2024Review
- Loss of β-cell identity and dedifferentiation, not an irreversible process?Frontiers in endocrinology · 2024Review
- The molecular determinants of phenotypic plasticity in homeostasis and neoplasia.Cancer heterogeneity and plasticity · 2024Article
71 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
Regulation of cell differentiation programs requires complex interactions between transcriptional and epigenetic networks. Elucidating the principal molecular events responsible for the establishment and maintenance of cell fate identities will provide important insights into how cell lineages are specified and maintained and will improve our ability to recapitulate cell differentiation events in vitro. In this study, we demonstrate that Nkx2.2 is part of a large repression complex in pancreatic β cells that includes DNMT3a, Grg3, and HDAC1. Mutation of the endogenous Nkx2.2 tinman (TN) domain in mice abolishes the interaction between Nkx2.2 and Grg3 and disrupts β-cell specification. Furthermore, we demonstrate that Nkx2.2 preferentially recruits Grg3 and HDAC1 to the methylated Aristaless homeobox gene (Arx) promoter in β cells. The Nkx2.2 TN mutation results in ectopic expression of Arx in β cells, causing β-to-α-cell transdifferentiation. A corresponding β-cell-specific deletion of DNMT3a is also sufficient to cause Arx-dependent β-to-α-cell reprogramming. Notably, subsequent removal of Arx in the β cells of Nkx2.2(TNmut/TNmut) mutant mice reverts the β-to-α-cell conversion, indicating that the repressor activities of Nkx2.2 on the methylated Arx promoter in β cells are the primary regulatory events required for maintaining β-cell identity.
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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.