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Regulation of Epidermal Keratin Expression by Retinoic Acid and Thyroid Hormone
Author(s) -
Ohtsuki Mamitaro,
TomicCanic Marjana,
Freedberg Irwin M.,
Blumenberg Miroslav
Publication year - 1992
Publication title -
the journal of dermatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.9
H-Index - 65
eISSN - 1346-8138
pISSN - 0385-2407
DOI - 10.1111/j.1346-8138.1992.tb03779.x
Subject(s) - keratin , retinoic acid , keratin 6a , biology , keratin 8 , retinoic acid receptor , epidermis (zoology) , nuclear receptor , keratin 5 , microbiology and biotechnology , gene , thyroid hormone receptor , gene expression , intermediate filament , transcription factor , cell , genetics , cytoskeleton , anatomy
In the epidermis, retinoic acid (RA) is known to regulate the gene expression of keratins, the intermediate filament proteins of epithelial cells. We have cloned the upstream regulatory regions of three human epidermal keratin genes, K5, K10, and K14, and engineered DNA constructs in which these regions drive expression of the CAT reporter gene. By co‐transfecting the constructs into various epithelial cell types along with the vectors expressing the nuclear receptors for RA and thyroid hormone (T3), we have shown that RA and T3 directly regulate expression of these three keratin genes through the action of their nuclear receptors. In this paper, we review our previous results to stress that RA has a dual effect on keratin expression in epidermis: both direct and indirect. We also analyze the DNA sequences upstream from those three RA‐regulated keratin genes and identify the clusters of degenerate consensus half‐site motifs, which may comprise the putative retinoic acid recognition elements (RAREs). Furthermore, our recent results concerning the regulation of K5 and K14 expression by the RA receptor are also shown; these confirm our predictions regarding the location of the RAREs in epidermal keratin genes.