| 摘要 |
The present disclosure provides a detailed characterization of the sequences and factors controlling expression of a human gene expressed specifically in keratinocytes. Using 5' upstream sequence of the human K14 keratin gene coupled to one of two reporter genes, sequences necessary and sufficient for expression of K14 have been examined in both cultured human keratinocytes and in mitotically active basal keratinocytes of transgenic mouse epidermis. The existence of distal and proximal elements located 5' from the transcription initiation site of the hK14 gene is demonstrated, which when combined with a TATA box element, appear to act in concert to drive keratinocyte-specific expression. The proximal element was also examined. After using CAT assays to narrow the transcriptional activation element to within 110 bp, the existence of a keratinocyte nuclear factor was determined, termed KER1 (AP2), which binds to the 10 bp palindromic sequence, 5' G C C T G C A G G C 3', within this domain. The data suggest that both the sequence and the nuclear factor that has been identified are involved, in conjunction with a distal element (-1700 to -2100 of the human K14 gene) in controlling keratinocyte-specific expression in vitro and in vivo.
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