Comparison of chromatin remodeling and transcriptional activation of the mouse mammary tumor virus promoter by the androgen and glucocorticoid receptor
Hj. List et al., Comparison of chromatin remodeling and transcriptional activation of the mouse mammary tumor virus promoter by the androgen and glucocorticoid receptor, EXP CELL RE, 250(2), 1999, pp. 414-422
We examined the interaction between the androgen (AR) and glucocorticoid re
ceptor (GR) at the transcriptional level using mouse fibroblast cell lines
harboring an integrated mouse mammary tumor virus (MMTV) promoter. We found
that the AR, after induction with dihydrotestosterone (DHT), caused a prog
ressive increase in MMTV-CAT reporter activity over 72 h which was correlat
ed to an increase in chromatin remodeling of the MMTV promoter in the vicin
ity of the hormone response element (HRE). In contrast, stimulation of the
GR by the synthetic glucocorticoid dexamethasone (Dex) caused a transient i
ncrease in MMTV transcriptional activity which returned to basal levels aft
er 72 h. These changes were correlated to a transient increase in chromatin
remodeling in the region of the HRE. Neither cotreatment nor pretreatment
with Dex affected the DHT response. In fact, there was a more than additive
effect of the two hormones on transcription at early time points. This sug
gests that the inability of GR to remodel chromatin, after 24 h of hormone
treatment, is most likely related to changes in the GR itself and not the c
hromatin remodeling process. Consistent with this, nuclear GR levels droppe
d by greater than 50% after Dex treatment whereas the AR was induced fourfo
ld after 24 h of DHT treatment. We conclude that a promoter with an ordered
chromatin structure can still respond to androgens even after its glucocor
ticoid responsiveness is lost. This may be one mechanism cells utilize to e
stablish target gene specificity for nuclear receptors that recognize ident
ical DNA sequences. (C) 1999 Academic Press.