Glucocorticoid receptors recognize DNA sequences in and around murine mammary tumour virus DNA

In several rodent cell lines, glucocorticoids increase the transcription of murine mammary tumour virus (MMTV) proviral DNA in a process mediated by the glucocorticoid receptor. To investigate whether a direct interaction between the receptor and specific sequences on the induced genes can be implicated in the hormonal regulation of transcription, filter binding studies were performed with partially purified glucocorticoid receptor of rat liver and eight cloned MMTV proviral probes. Both the 40 000 and the 90 00 mol. wt. forms of the receptor do bind preferentially to restriction fragments containing the right 400-500 nucleotides of the MMTV long terminal repeat units (LTR). Using LTR deletion mutants, we confirm that the right end of the LTR contains at least one binding site for the glucocorticoid receptor. In addition, the receptor binds preferentially to the mouse genomic sequences flanking at least three endogenous proviral copies, and to sequences within the env genes in some of the endogenous and exogenous proviruses. These findings are compatible with the hypothesis that steroid hormones regulate specific gene expression through a direct interaction of the hormone-receptor complex with DNA sequences in and around the induced genes.