Glucocorticoids are important regulators of skin tissue. Radoja et al. studied the ability of glucocorticoids to repress transcription of acidic keratins, K14, K16, and K17, and basic keratins, K5 and K6. Analysis of the promoters identified two unique consensus negative glucocorticoid response elements (nGRE) for the basic and acidic keratins. Based on gel-shift assays and DNA footprinting, the nGREs bound four monomers of glucocorticoid receptor and based on keratin-promoter assays in transfected cells, transcriptional repression required all four sites to be occupied. Furthermore, histone acetylases (HAT and CBP), typically associated with gene activation, were able to enhance the suppression of transcription mediated by the glucocorticoids suggesting a role for histone acetylases in transcriptional repression.
Radoja, N., Komine, M., Jho, S.H., Blumenberg, M., and Tomic-Canic, M. (2000) Novel mechanism of steroid action in skin through glucocorticoid receptor monomers. Mol. Cell. Biol. 20: 4328-4339. [Abstract] [Full Text]