DIFFERENTIAL STEROID-HORMONE INDUCTION OF TRANSCRIPTION FROM THE MOUSE MAMMARY-TUMOR VIRUS PROMOTER

The Mouse Mammary Tumor Virus (MMTV) contains sequences in its proxima l promoter region to which both glucocorticoid and progesterone recept ors can bind. In transient transfection experiments both hormones are able to stimulate transcription from reporter plasmids containing eith er native or consensus hormone response elements (glucocorticoid respo nse element/progesterone response element). Previous experiments have demonstrated that the MMTV long terminal repeat is reproducibly assemb led into a phased array of nucleosomes when stably introduced into cel ls. Stimulation by glucocorticoids of endogenous templates led to a ra pid but transient increase in transcription initiation and mRNA accumu lation that can be correlated with increased sensitivity to restrictio n enzymes. In contrast, experiments using progesterone or a truncated glucocorticoid receptor failed to elicit a similar increase in mRNA le vels as dexamethasone from stable chromatin templates. In an attempt t o understand this differential response, we have compared the responsi veness of the MMTV promoter to glucocorticoids and progesterone when i t is organized in either stable chromatin or in transiently acquired p lasmids. Our results demonstrate that the native chromatin structure p revents activation of this locus by progesterone, but permits stimulat ion by glucocorticoids.