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ESE-1 (Epithelium-Specific Ets) is a novel, highly tissue-restricted member of the ets transcription factor/oncogene family, which has features distinct from those of any other ets-related factor. ESE-1 binds with high affinity to and transactivates the ets binding site in the promoter of the keratinocyte terminal differentiation marker gene, SPRR2A. ESE-1 is a critical regulator of epithelial cell differentiation.