This SB203580 sequence-directed arrangement of nucleosomes is likely to Masitinib abmole bioscience directly impact transcription, since functional transcription factor binding sites were much more frequently found in linker regions than in DNA covered by nucleosomes, and since start sites of active genes were frequently devoid of nucleosomes. These genomic mapping approaches can also be used to relate changes in nucleosome positions with changes in gene expression. For instance, two recent studies in yeast showed that heat shock gene activation was frequently associated with decreased nucleosome occupancy over start sites, while repression was associated with increased occupancy, effects which were often dependent on yeast SWI/SNF function and correlated with SWI/ SNF binding. These studies indicate that nucleosome positioning will be involved in transcriptional regulation much more often than was initially suspected, and emphasize the need for a deeper understanding of how nucleosome positions are functionally controlled. Glucocorticoid agonists are some of the most commonly prescribed drugs to treat inflammation and a variety of immune disorders. Binding of cortisol, dexamethasone or other glucocorticoid agonists causes a conformational change in the Glucocorticoid Receptor, releasing it from cytoplasmic heat shock proteins, allowing it to dimerize, translocate into the nucleus and bind to glucocorticoid response elements at target gene loci. Hormone binding also facilitates interaction with coactivator complexes including the ATP-dependent chromatin remodeling complex, SWI/SNF. Recent studies have identified a growing number of genes that are directly activated or repressed by binding of dexamethasonebound GR. In most cases, however, little is known about the chromatin structure of these genes�� promoters or remodeling events that accompany GR binding. Some clues do exist, however. For instance, introduction of functional human SWI/SNF into cells that lack it greatly increased the accessibility of DNA normally covered by one Mouse Mammary Tumor Virus promoter nucleosome, Nuc B, which occupies the promoter from,2250 to 2100 and covers GRE elements as well as an essential NF1 binding site. In addition, one recent study examined DNase hypersensitive sites on ten mouse genes that were either activated or repressed by GR, most of which were also regulated by SWI/SNF. The results showed that GR- and/or hSWI/SNF-dependent increases in DNase sensitivity were found at many of these loci, frequently mapping near GR binding sites. These and other studies indicate that chromatin changes, driven at least in part by hSWI/SNF, are important aspects of gene regulation by GR. However, the specific nature of these changes is largely unknown.