酵母转录因子Gal4研究进展

胁迫应答基因的转录激活是细胞应答胁迫作用的关键步骤。转录激活因子与启动子顺式作用元件结合是胁迫应答基因转录激活的关键环节。进化保守的Gal4是半乳糖代谢相关基因的转录激活因子。酵母Gal4通过其N端的DNA结合结构域识别并结合启动子UAS,通过其C端的激活结构域与转录因子作用,起始RNA聚合酶Ⅱ复合体的组装和转录。该过程不仅受转录调控因子Gal80和Gal3的调节,还与Gal4二聚体的形成有关。概述了酵母半乳糖代谢相关基因转录激活因子Gal4的研究进展。     

Peptides selected to bind the Gal80 repressor are potent transcriptional activation domains in yeast

The activation domain of the yeast Gal4 protein binds specifically to the Gal80 repressor and is also thought to associate with one or more coactivators in the RNA polymerase II holoenzyme and chromatin remodeling machines. This is a specific example of a common situation in biochemistry where a single protein domain can interact with multiple partners. Are these different interactions related chemically? To probe this point, phage display was employed to isolate peptides from a library based solely on their ability to bind Gal80 protein in vitro. Peptide-Gal80 protein association is shown to be highly specific and of moderate affinity. The Gal80 protein-binding peptides compete with the native activation domain for the repressor, suggesting that they bind to the same site. It was then asked if these peptides could function as activation domains in yeast when tethered to a DNA binding domain. Indeed, this is the case. Furthermore, one of the Gal80-binding peptides binds directly to a domain of the Gal11 protein, a known coactivator. The fact that Gal80-binding peptides are functional activation domains argues that repressor binding and activation/coactivator binding are intimately related properties. This peptide library-based approach should be generally useful for probing the chemical relationship of different binding interactions or functions of a given native domain.