ArticleThe Journal of biological chemistry2008
Pdx1 and BETA2/NeuroD1 participate in a transcriptional complex that mediates short-range DNA looping at the insulin gene.
Article in The Journal of biological chemistry, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 46 citations in OpenAlex.
- PDX1 phosphorylation at S61 by mTORC1 links nutrient signaling to β cell function and metabolic disease.Cell reports · 2026Article
- Endocrine-related neurological function recovery in pancreatic transplantation.World journal of transplantation · 2025Article
- Beta cell-specific PAK1 enrichment ameliorates diet-induced glucose intolerance in mice by promoting insulin biogenesis and minimising beta cell apoptosis.Diabetologia · 2025Article
- NEUROD1 reinforces endocrine cell fate acquisition in pancreatic development.Nature communications · 2023Article
- Multidimensional scaling methods can reconstruct genomic DNA loops using Hi-C data properties.PloS one · 2023Article
- Amino acids-Rab1A-mTORC1 signaling controls whole-body glucose homeostasis.Cell reports · 2021Article
- Article
- Pax4 synergistically acts with Pdx1, Ngn3 and MafA to induce HuMSCs to differentiate into functional pancreatic β-cells.Experimental and therapeutic medicine · 2019Article
- Disruption of CTCF-YY1-dependent looping of the human papillomavirus genome activates differentiation-induced viral oncogene transcription.PLoS biology · 2018Article
- Transcriptional activity of the islet β cell factor Pdx1 is augmented by lysine methylation catalyzed by the methyltransferase Set7/9.The Journal of biological chemistry · 2015Article
- Article
- Transient pairing of homologous Oct4 alleles accompanies the onset of embryonic stem cell differentiation.Cell stem cell · 2015Article
- Article
- Mapping Mammalian Cell-type-specific Transcriptional Regulatory Networks Using KD-CAGE and ChIP-seq Data in the TC-YIK Cell Line.Frontiers in genetics · 2015Article
- The study of regulatory effects of Pdx-1, MafA and NeuroD1 on the activity of porcine insulin promoter and the expression of human islet amyloid polypeptide.Molecular and cellular biochemistry · 2014Article
- Regulation of human CYP2C9 expression by electrophilic stress involves activator protein 1 activation and DNA looping.Molecular pharmacology · 2014Article
- An amino terminal phosphorylation motif regulates intranuclear compartmentalization of Olig2 in neural progenitor cells.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2014Article
- SH2B1 in β-cells promotes insulin expression and glucose metabolism in mice.Molecular endocrinology (Baltimore, Md.) · 2014Article
- Separated at birth? The functional and molecular divergence of OLIG1 and OLIG2.Nature reviews. Neuroscience · 2012Review
- Chromatin structure, epigenetic mechanisms and long-range interactions in the human insulin locus.Diabetes, obesity & metabolism · 2012Review
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
The activity of the insulin gene, Ins, in islet beta cells is thought to arise in part from the synergistic action of the transcription factors Pdx1 and BETA2/NeuroD1. We asked how the binding of these factors to A and E elements many tens or hundreds of base pairs upstream of the start site could influence activity of transcriptional machinery. We therefore tested the hypothesis that the complex of Pdx1 and BETA2/NeuroD1 maintains a DNA conformation such that distal regions of the gene are brought into proximity of the promoter and coding region. We show by coimmunoprecipitation that Pdx1 and BETA2/NeuroD1 exist within a complex and that the two physically interact with one another in this complex as assessed by fluorescence resonance energy transfer. Consistent with this interaction, we found that the two factors simultaneously occupy the same fragment of the Ins gene in beta cell lines using the chromatin immunoprecipitation/re-chromatin immunoprecipitation assay. Using a modification of the chromosome conformation capture assay in vitro and in beta cells, we observed that Pdx1 and BETA2/NeuroD1 mediate looping of a segment of Ins that brings EcoRI sites located at -623 and +761 bp (relative to the transcriptional start site) in proximity to one another. This looping appears to be dependent in vitro upon an intact A3 binding element, but not upon the E2 element. Based on our findings, we propose a model whereby Pdx1 and BETA2/NeuroD1 physically interact to form a nucleoprotein complex on the Ins gene that mediates formation of a short DNA loop. Our results suggest that such short loop conformations may be a general mechanism to permit interactions between transcription factors and basal transcriptional machinery.
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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.