Differential steroid hormone induction of transcription from the mouse mammary tumor virus promoter.

Abstract

The Mouse Mammary Tumor Virus (MMTV) contains sequences in its proximal promoter region to which both glucocorticoid and progesterone receptors can bind. In transient transfection experiments both hormones are able to stimulate transcription from reporter plasmids containing either native or consensus hormone response elements (glucocorticoid response element/progesterone response element). Previous experiments have demonstrated that the MMTV long terminal repeat is reproducibly assembled into a phased array of nucleosomes when stably introduced into cells. Stimulation by glucocorticoids of endogenous templates led to a rapid but transient increase in transcription initiation and mRNA accumulation that can be correlated with increased sensitivity to restriction enzymes. In contrast, experiments using progesterone or a truncated glucocorticoid receptor failed to elicit a similar increase in mRNA levels as dexamethasone from stable chromatin templates. In an attempt to understand this differential response, we have compared the responsiveness of the MMTV promoter to glucocorticoids and progesterone when it is organized in either stable chromatin or in transiently acquired plasmids. Our results demonstrate that the native chromatin structure prevents activation of this locus by progesterone, but permits stimulation by glucocorticoids.

Dynamic access of the glucocorticoid receptor to response elements in chromatin

“…The response of the MMTV promoters within the amplified arrays has been rigorously characterized (Fragoso et al, 1998; Kramer et al, 1999) and it was shown that the chromatin reorganization event summed over the individual promoter copies in the array is indistinguishable from the event averaged over many cells with single gene copies. Additionally, it has been established that the kinetics of the receptor induced transcription observed in the array cells is also identical to that originally described in low copy cells (Archer et al, 1994; Smith et al, 1997). …”

Identification of domains of c-Jun mediating androgen receptor transactivation

“…These receptors form a subfamily within the nuclear receptor superfamily that is capable of recognizing a common DNA sequence (Ham et al, 1988;Arriza et al, 1987). While a number of genes have been shown to be activated by more than one receptor within this family, recent studies have identi®ed several genes that are activated speci®cally by AR (Claessens et al, 1996;Alder et al, 1992) or GR (Archer et al, 1994). How gene-speci®c activation by AR or GR occurs is not presently understood, but several possible mechanisms have been proposed.…”

“…How gene-speci®c activation by AR or GR occurs is not presently understood, but several possible mechanisms have been proposed. These include promoter-speci®c elements¯anking and interacting with the hormone-response elements (HREs) that bind nuclear receptors (Scarlett and Robins 1995), di erential chromatin e ects on receptor activity (Archer et al, 1994), or receptor interaction with distinct accessory factors (reviewed in Beato et al, 1995). Nuclear receptors are known to interact with a variety of accessory factors.…”

Transactivation Specificity of Glucocorticoid VersusProgesterone Receptors

“…Chromatin architecture has recently emerged as another promising modifier for receptor-regulated expression of some, but not all (10), genes. Chromatin structure can repress gene expression (11,12), thereby increasing the fold induction by receptor-steroid complexes, especially in cell-free systems (13,14).…”

“…Chromatin structure can repress gene expression (11,12), thereby increasing the fold induction by receptor-steroid complexes, especially in cell-free systems (13,14). Chromatin environment can control gene inducibility by PR (15)(16)(17), and chromatin structure has been proposed to be a determinant for PR induction (10,15). However, alterations in chromatin structure do not appear to be a prerequisite for all steroid receptor-induced gene transactivation.…”