ESE-3, a novel member of an epithelium-specific Ets transcription factor subfamily, demonstrates different target gene specificity from ESE-1

Most cancers originate as a result of aberrant gene expression in mainly gl andular epithelial tissues leading to defects in epithelial cell differenti ation. The latter is governed by distinct sets of transcriptional regulator s. Here we report the characterization of epithelium-specific Ets factor, f amily member 3 (ESE-3), a novel member of the ESE subfamily of Ets transcri ption factors. ESE-3 shows highest homology to two other epithelium restric ted Ets factors, ESE-1 and ESE-2. ESE-3, like ESE-1 and ESE-2, is exclusive ly expressed in a subset of epithelial cells with highest expression in gla ndular epithelium such as prostate, pancreas, salivary gland, and trachea. A potential role in branching morphogenesis is suggested, since ESE-3 trans activates the c-MET promoter via three high affinity binding sites. Additio nally, ESE-3 binding to DNA sequences in the promoters of several glandular epithelium-specific genes suggests a role for ESE-3 in later stages of gla ndular epithelium differentiation. Although ESE-3 and ESE-1 bind with simil ar affinity to various Ets binding sites, ESE-3 and ESE-1 differ significan tly in their ability to transactivate the promoters containing these sites. Our results support the notion that ESE-1, ESE-2, and ESE-3 represent a un ique epithelium-specific subfamily of Ets factors that have critical but di stinct functions in epithelial cell differentiation and proliferation.