ArticleGenes & development2001
Pax6 and SOX2 form a co-DNA-binding partner complex that regulates initiation of lens development.
Article in Genes & development, 2001. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 145 papers.
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Who cites it
145 citing papers in PubMed, 399 citations in OpenAlex.
- Lens aging and disease: Molecular mechanisms, functional consequences, and pharmacological implications.Progress in retinal and eye research · 2026Review
- dentification and characterization of novelBMJ open diabetes research & care · 2025Article
- The Systemic Genotype-Phenotype Characterization of PAX6-Related Eye Disease in 164 Chinese Families.Investigative ophthalmology & visual science · 2024Article
- RNA Binding Properties of SOX Family Members.Cells · 2024Article
- Deep mutational scanning quantifies DNA binding and predicts clinical outcomes of PAX6 variants.Molecular systems biology · 2024Article
- Analysis of long-range chromatin contacts, compartments and looping between mouse embryonic stem cells, lens epithelium and lens fibers.Epigenetics & chromatin · 2024Article
- A bibliometric and visualized analysis of the pathogenesis of cataracts from 1999 to 2023.Heliyon · 2024Article
- Phase separation as a possible mechanism for dosage sensitivity.Genome biology · 2024Article
- Integrated single-cell multiomics uncovers foundational regulatory mechanisms of lens development and pathology.Development (Cambridge, England) · 2024Article
- Enhancer Activation by Transcription Factors and Underlying Mechanisms.Results and problems in cell differentiation · 2024Article
- Article
- Multiomics Analysis Reveals Novel Genetic Determinants for Lens Differentiation, Structure, and Transparency.Biomolecules · 2023Review
- Making a head: Neural crest and ectodermal placodes in cranial sensory development.Seminars in cell & developmental biology · 2023Review
- Novel Mutations of PAX6 and WFS1 Associated With Congenital Cataract in a Chinese Family.Cureus · 2023Article
- Identification of PAX6 and NFAT4 as the Transcriptional Regulators of the Long Noncoding RNA Mrhl in Neuronal Progenitors.Molecular and cellular biology · 2022Article
- Cell fate decisions, transcription factors and signaling during early retinal development.Progress in retinal and eye research · 2022Review
- Variants in PAX6, PITX3 and HSF4 causing autosomal dominant congenital cataracts.Eye (London, England) · 2022Article
- Formation of three-dimensional cell aggregates expressing lens-specific proteins in various cultures of human iris-derived tissue cells and iPS cells.Experimental and therapeutic medicine · 2022Article
- Sox8 remodels the cranial ectoderm to generate the ear.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Characterization of Associated Nonclassical Phenotypes in Patients with Deletion in the WAGR Region Identified by Chromosomal Microarray: New Insights and Literature Review.Molecular syndromology · 2022Article
85 more citing papers are in PubMed but not listed here.
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Pax6 is a key transcription factor in eye development, particularly in lens development, but its molecular action has not been clarified. We demonstrate that Pax6 initiates lens development by forming a molecular complex with SOX2 on the lens-specific enhancer elements, e.g., the delta-crystallin minimal enhancer DC5. DC5 shows a limited similarity to the binding consensus sequence of Pax6 and is bound poorly by Pax6 alone. However, Pax6 binds cooperatively with SOX2 to the DC5 sequence, resulting in formation of a high-mobility form of ternary complex in vitro, which correlates with the enhancer activation in vivo. We observed Pax6 and SOX2-interdependent factor occupancy of DC5 in a chromatin environment in vivo, providing the molecular basis of synergistic activation by Pax6 and SOX2. Subtle alterations of the Pax6-binding-site sequence of DC5 or of the inter-binding-sites distance diminished the cooperative binding and caused formation of a non-functional low-mobility form complex, suggesting DNA sequence-guided and protein interaction-induced conformation change of the Pax6 protein. When ectopically expressed in embryo ectoderm, Pax6 and SOX2 in combination activate delta-crystallin gene and elicit lens placode development, indicating that the complex of Pax6 and SOX2 formed on specific DNA sequences is the genetic switch for initiation of lens differentiation.
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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.