The role of calcium-responsive element located in human keratin 1 gene on keratinocyte differentiation

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The mammalian epidermis is a constantly renewing stratified squamous epithelium. The major cell type of the epidermis is the epidermal keratinocyte. Keratinocytes undergo a strictly regulated, highly compartmentalized differentiation process that results in a mature stratified epidermis. The basal layer of the epidermis contains proliferating keratinocytes. In response to differentiating signals, these cells stop dividing and simultaneously mature and migrate through the spinous and granular layers of the epidermis. Ultimately, they are transformed into flattened squamas and sloughed into the environment. Expression of the Keratin 1 (K1) gene is tightly regulated and is coincident with a distinct differentiation state of keratinocytes. Transcription of K1 is primarily localized to the spinous layer. Evaluation of approximately 6 kb of 5' franking sequence indicated that these sequences possessed the information required for tissue-and differentiation-specific expression. Investigation of distal sequences identified Sp 1 site. Mutation of either of these sites, which ablated binding, resulted in significant decreases in promoter activity. Sequences containing the distal element, while required for high levels of expression, were responsible for significant suppression in the presence of Sp1. Collectively, these data identify and characterize several regulatory elements that cooperate to cause the appropriate tissue-, developmental-, and differentiation-specific expression of the hK1 gene.