期刊名称:Proceedings of the National Academy of Sciences
印刷版ISSN:0027-8424
电子版ISSN:1091-6490
出版年度:1991
卷号:88
期号:19
页码:8283-8287
DOI:10.1073/pnas.88.19.8283
语种:English
出版社:The National Academy of Sciences of the United States of America
摘要:Induction of transcription from a promoter with two upstream glucocorticoid response elements is 10- to 20-fold greater than that from a similar promoter with only one response element. We have shown that interactions involving the major transactivation domain of the glucocorticoid receptor (tau 1) are the sole determinant of such synergistic transactivation by the receptor. The other transactivation domain of the receptor (tau 2) did not mediate synergistic transactivation, and therefore the ability to synergize is operationally distinct from the transactivation function per se. The level of synergistic transactivation observed in vivo can be accounted for by the level of cooperative DNA binding seen in vitro for a glucocorticoid receptor derivative containing only the tau 1 and DNA-binding domains. Cooperative DNA binding was also observed using a tau 1-DNA-binding domain protein, which was expressed in Escherichia coli and extensively purified. Therefore, it is likely that direct protein-protein interactions between tau 1 domains mediate the cooperative DNA binding. The role of cooperative DNA binding for synergistic transactivation in vivo is discussed in relation to other possible mechanisms.