The tight junction protein ZO-1 and an interacting transcription factor regulate ErbB-2 expression.
Epithelial tight junctions regulate paracellular diffusion and restrict the intermixing of apical and basolateral plasma membrane components. We now identify a Y-box transcription factor, ZONAB (ZO-1-associated nucleic acid-binding protein), that binds to the SH3 domain of ZO-1, a submembrane protein of tight junctions. ZONAB localizes to the nucleus and at tight junctions, and binds to sequences of specific promoters containing an inverted CCAAT box. In reporter assays, ZONAB and ZO-1 functionally interact in the regulation of the ErbB-2 promoter in a cell density-dependent manner. In stably transfected overexpressing cells, ZO-1 and ZONAB control expression of endogenous ErbB-2 and function in the regulation of paracellular permeability. These data indicate that tight junctions directly participate in the control of gene expression and suggest that they function in the regulation of epithelial cell differentiation.
Balda
M S
MS
Department of Cell Biology, University of Geneva, 30, Quai Ernest-Ansermet, 1211 Genève-4, Switzerland. Balda@cellbio.unige.ch
Matter
K
K
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D002452:Cell Count; D002460:Cell Line; D002463:Cell Membrane Permeability; D002467:Cell Nucleus / Q000737:chemistry; D003001:Cloning, Molecular; D004247:DNA / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D004285:Dogs; D005786:Gene Expression Regulation; D018816:Genes, cdc; D018734:Genes, erbB-2 / Q000235:genetics*; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D010750:Phosphoproteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011233:Precipitin Tests; D011401:Promoter Regions, Genetic / Q000235:genetics; D011485:Protein Binding; D019108:Tight Junctions / Q000737:chemistry*; D014157:Transcription Factors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D014162:Transfection; D062826:Zonula Occludens-1 Protein; D018909:src Homology Domains
D004268:DNA-Binding Proteins; D008565:Membrane Proteins; D010750:Phosphoproteins; D014157:Transcription Factors; C409302:ZONAB protein, Canis familiaris; D062826:Zonula Occludens-1 Protein; D004247:DNA