Recruitment of chromatin remodelling factors during gene activation via the glucocorticoid receptor N-terminal domain

We have shown that yeast mutants with defects in the Ada adaptor proteins a re defective in hormone-dependent gene activation by ectopically expressed human glucocorticoid receptor (GR). Others have shown that the Ada2 protein is required for physical interactions between some activation domains and TBP (TATA-binding protein), whereas the Gcn5 (Ada4) protein has a histone a cetyltransferase (HAT) activity. Although all HAT enzymes are able to acety late histone substrates, some also acetylate non-histone proteins. Taken to gether, these observations suggest that the Ada proteins have the ability t o effect different steps in the process of gene activation. It has recently been shown that the Ada proteins are present in two distinct protein compl exes, the Ada complex and a larger SAGA complex. Our recent work has focuse d on determining (1) which of the Ada-containing complexes mediates gene ac tivation by GR, (2) whether the HAT activity encoded by GCN5 is required fo r GR-dependent gene activation, (3) whether the Ada proteins contribute to GR-mediated activation at the level of chromatin remodelling and (4) how th e role of these HAT complexes is integrated with other chromatin remodellin g activities during GR-mediated gene activation. Our results suggest a mode l in which GR recruits the SAGA complex and that this contributes to chroma tin remodelling via a mechanism involving the acetylation of histones. Furt hermore, recruitment of the SWI/SNF remodelling complex also has a role in GR-mediated activation that is independent of the role of SAGA. These compl exes are similar to analogous mammalian complexes and therefore these resul ts are likely to be relevant to the human sv stem.