EXPRESSION, STRUCTURE AND FUNCTION OF FILAGGRIN

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Filaggrin, the processed form of profilaggrin, is a major product of terminally differentiating mammalian epidermis. Based on in vitro experiments, filaggrin is thought to be involved in the aggregation and specific alignment of keratin intermediate filaments during the final stages of development in the epidermis in vivo. We have explored the regulation of expression of the profilaggrin gene and have characterized the proximal promoter. An AP1 site and its cognate binding c-fos and c-jun proteins confer keratinocyte-specific expression to the gene, in concert with neighboring Sp1, ets-like, and NF-kB elements. We have discovered a novel ets transcription protein that seems to function in the regulation of expression of several late differentiation genes in the epidermis, including profilaggrin.