Yoshinaga S K, Peterson C L, Herskowitz I, Yamamoto K R
Department of Biochemistry and Biophysics, University of California, San Francisco 94143-0448.
Science. 1992 Dec 4;258(5088):1598-604. doi: 10.1126/science.1360703.
The SWI1, SWI2, and SWI3 proteins, which are required for regulated transcription of numerous yeast genes, were found also to be essential for rat glucocorticoid receptor function in yeast; the receptor failed to activate transcription in strains with mutations in the SWI1, SWI2, or SWI3 genes. Certain mutations in genes encoding components of chromatin, identified as suppressors of swi mutations, partially relieved the SWI- requirement for receptor function. Immunoprecipitation of glucocorticoid receptor derivatives from wild-type (SWI+) yeast extracts coprecipitated the SWI3 protein; such receptor-SWI3 complexes were not detected in swi1- or swi2- mutant strains, implying that a complex of multiple SWI proteins may associate with the receptor. Prior incubation of a Drosophila embryo transcription extract with the yeast SWI3-specific antibody inhibited receptor function in vitro whereas the antibody had no effect if added after initiation complex formation. Thus, positive regulation by the glucocorticoid receptor in vivo and in vitro appears to require its interaction, at an early step, with one or more SWI proteins.
SWI1、SWI2和SWI3蛋白是众多酵母基因转录调控所必需的，研究发现它们对于大鼠糖皮质激素受体在酵母中的功能也是必不可少的；在SWI1、SWI2或SWI3基因发生突变的菌株中，该受体无法激活转录。某些编码染色质成分的基因中的突变被鉴定为swi突变的抑制子，部分缓解了受体功能对SWI的需求。从野生型（SWI+）酵母提取物中免疫沉淀糖皮质激素受体衍生物时，共沉淀出SWI3蛋白；在swi1或swi2突变菌株中未检测到这种受体-SWI3复合物，这意味着多种SWI蛋白的复合物可能与受体相关联。用酵母SWI3特异性抗体预先孵育果蝇胚胎转录提取物会在体外抑制受体功能，而如果在起始复合物形成后添加该抗体则没有效果。因此，糖皮质激素受体在体内和体外的正调控似乎在早期阶段就需要其与一种或多种SWI蛋白相互作用。
