119 research outputs found

    Glucocorticoid Receptor–Promoter Interactions: Energetic Dissection Suggests a Framework for the Specificity of Steroid Receptor-Mediated Gene Regulation

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    The glucocorticoid receptor (GR) is a member of the steroid receptor family of ligand-activated transcription factors. A number of studies have shown that steroid receptors regulate distinct but overlapping sets of genes; however, the molecular basis for such specificity remains unclear. Previous work from our laboratory has demonstrated that under identical solution conditions, three other steroid receptors [the progesterone receptor A isoform (PR-A), the progesterone receptor B isoform (PR-B), and estrogen receptor α (ER-α)] differentially partition their self-association and promoter binding energetics. For example, PR-A and PR-B generate similar dimerization free energies but differ significantly in their extents of intersite cooperativity. Conversely, ER-α maintains an intersite cooperativity most comparable to that of PR-A yet dimerizes with an affinity orders of magnitude greater than that of either of the PR isoforms. We have speculated that these differences serve to generate receptor-specific promoter occupancies, and thus receptor-specific gene regulation. Noting that GR regulates a unique subset of genes relative to the other receptors, we hypothesized that the receptor should maintain a unique set of interaction energetics. We rigorously determined the self-association and promoter binding energetics of full-length, human GR under conditions identical to those used in our earlier studies. We find that unlike all other receptors, GR shows no evidence of reversible self-association. Moreover, GR assembles with strong intersite cooperativity comparable to that seen only for PR-B. Finally, simulations show that such partitioning of interaction energetics allows for receptor-specific promoter occupancies, even under conditions where multiple receptors are competing for binding at identical sites

    Responses of two Mediterranean seagrasses to experimental changes in salinity

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    The aim of this study is to examine the effects of variations in salinity levels on growth and survival of two fast-growing Mediterranean seagrasses, Cymodocea nodosa and Zostera noltii. We also tested the capacity of C. nodosa to acclimate to a gradual increase in salinity and to discover how it responds to a sharp rise in salinity in combination with other factors, such as increases in temperature, seasonality and different plant-population origins. Several short-term (10 days) experiments were conducted under controlled conditions. For each experiment, ten marked shoots were placed in 5-l aquaria, where they were exposed to different salinity treatments (ranging from 2 to 72 psu). Growth and survival of both species were significantly affected by salinity. A significant effect between salinity and temperature on the shoot growth rate of C. nodosa was also detected, but not on shoot mortality. When C. nodosa plants were acclimated by gradually increasing the salinity level, it was observed that acclimatisation improved tolerance to salinity changes. A different response to salinity variations, depending on the origin of the plants or the season of the year, was also detected. These results indicated that Z. noltii plants tolerate conditions of hyposalinity better than C. nodosa, and that the tolerance range of C. nodosa may change depending on the temperature, the season or the population.This research was financed by an ACUAMED contract and by an FPI grant (FPI 01 A 002) from the Generalitat Valenciana
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