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During development and differentiation, the expression of transcription factors is regulated in a temporal fashion. Newly expressed transcription factors must interact productively with target genes organized in chromatin. Although the mechanisms governing factor binding to chromatin templates are not well understood, it is now clear that template access can be dramatically influenced by nucleoprotein structure. We have examined the ability of a well characterized transactivator, the progesterone receptor (PR), to activate the mouse mammary tumor virus (MMTV) promoter organized either in stable, replicating templates that have a highly ordered nucleosome structure or as transiently transfected DNA, which adopts a less-defined structure. If the PR is transiently expressed in cells harboring both replicated and transient MMTV receptor constructs, it cannot significantly activate the stable replicated MMTV template. In contrast, when PR cDNA is stably inserted into the same cells and constitutively expressed, it gains the ability to activate both chromosomal and transiently introduced templates. These results demonstrate that newly expressed PR is not competent to activate the MMTV template in its native nucleoprotein conformation but acquires this ability upon prolonged expression in replicating cells.
Smith et al. (Wed,) studied this question.