标题:Identification and characterization of a cis-acting element that interferes with glucocorticoid-inducible activation of the mouse mammary tumor virus promoter.
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:12
页码:5393-5397
DOI:10.1073/pnas.88.12.5393
语种:English
出版社:The National Academy of Sciences of the United States of America
摘要:The rat hepatoma cell line M1.19 is stably infected by the mouse mammary tumor virus (MMTV), and the expression of the virus is induced by glucocorticoid treatment. However, in the 6.10.2 variant of M1.19, an increase in MMTV transcription is hardly detectable upon exposure to hormone. The mechanism of hormone-unresponsiveness in these cells has been unclear. In this study, we show that nuclear extract from 6.10.2 cells contains a specific DNA-binding activity that recognizes a sequence motif extending from positions -163 to -147 on the MMTV promoter. An oligonucleotide probe spanning this region binds a nuclear factor distinct from the glucocorticoid receptor. In vivo competition experiments, where increased amounts of a plasmid containing this element were transfected into 6.10.2 cells, showed a dose-dependent increase in hormonal inducibility of MMTV expression. Together, these results indicate that this sequence motif negatively modulates glucocorticoid-inducible activation of the MMTV promoter. Moreover, we have characterized a nuclear factor that preferentially binds to the coding strand of this element.