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 i dentify a Y-bos transcription factor, ZONAB (<(ZO)under bar>-1-associated n ucleic acid-binding protein), that binds to the SH3 domain of ZO-1, a subme mbrane protein of tight junctions. ZONAB localizes to the nucleus and at ti ght junctions, and binds to sequences of specific promoters containing an i nverted CCAAT hox. In reporter assays, ZONAB and ZO-1 functionally interact in the regulation of the ErbB-2 promoter in a cell density-dependent manne r. In stably transfected over-expressing cells, ZO-1 and ZONAB control expr ession 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 re gulation of epithelial cell differentiation.