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The tight junction protein ZO-1 and an interacting transcription factor regulate ErbB-2 expression
1Department of Cell Biology, University of Geneva, 30, Quai Ernest-Ansermet, 1211 Genève-4, Switzerland. Balda@cellbio.unige.ch
The EMBO Journal
|May 3, 2000
Summary
Researchers discovered ZONAB (ZO-1-associated nucleic acid-binding protein), a Y-box transcription factor that binds to ZO-1. This interaction regulates gene expression and epithelial cell differentiation via tight junctions.
Area of Science:
- Cell Biology
- Molecular Biology
- Epithelial Biology
Background:
- Epithelial tight junctions control paracellular diffusion and membrane component segregation.
- The molecular mechanisms underlying tight junction function in gene regulation are not fully understood.
Purpose of the Study:
- To identify novel proteins involved in tight junction regulation.
- To elucidate the role of ZONAB in tight junction-mediated gene expression and epithelial cell differentiation.
Main Methods:
- Y-box transcription factor screening.
- Protein-protein interaction assays (SH3 domain binding).
- Reporter gene assays for promoter activity.
- Stable cell transfection and overexpression studies.
- Measurement of paracellular permeability.
Main Results:
- Identified ZONAB, a Y-box transcription factor, binding to the SH3 domain of ZO-1.
- ZONAB localizes to the nucleus and tight junctions, binding to inverted CCAAT box sequences.
- ZONAB and ZO-1 functionally interact to regulate the ErbB-2 promoter in a cell density-dependent manner.
- Overexpression of ZO-1 and ZONAB controls endogenous ErbB-2 expression and paracellular permeability.
Conclusions:
- Tight junctions directly participate in the control of gene expression.
- ZONAB and ZO-1 interaction is crucial for regulating epithelial cell differentiation.
- This study reveals a novel mechanism linking cell adhesion structures to transcriptional control.