Steroid-selective initiation of chromatin remodeling and transcriptional activation of the mouse mammary tumor virus promoter is controlled by the site of promoter integration.

The mouse mammary tumor virus (MMTV) promoter has target sequences recognized by several steroid receptors. We present evidence for a novel mechanism that confers hormone specificity to this promoter. We show that remodeling of MMTV chromatin and the concomitant activation of the MMTV promoter are induced equally by glucocorticoids and progestins in one chromosomal context but are selective for glucocorticoids in another. Furthermore, increased histone acetylation modulates MMTV promoter regulation disparately at the two chromosomal locations. Together, these data indicate that chromosomal architecture commands a crucial role in gene regulation, imposing locus-specific selectivity between regulators with similar sequence recognition.