PMID- 7797076
OWN - NLM
STAT- MEDLINE
DCOM- 19950731
LR  - 20190516
IS  - 0890-9369 (Print)
IS  - 0890-9369 (Linking)
VI  - 9
IP  - 11
DP  - 1995 Jun 1
TI  - Dissection of progesterone receptor-mediated chromatin remodeling and 
      transcriptional activation in vivo.
PG  - 1366-76
AB  - We have investigated whether constitutive binding by the progesterone receptor 
      (PR) to a promoter is required for the maintenance of an open chromatin structure 
      in vivo. For these experiments, we used human T47D breast cancer cells in which 
      the mouse mammary tumor virus (MMTV) promoter, stably assembled as chromatin, is 
      constitutively hypersensitive to endonucleolytic cleavage. In vivo footprinting 
      revealed that transcription factors nuclear factor 1 and the PR were 
      constitutively bound to the MMTV promoter in these cells. Treatment of these 
      cells for 1 hr with the steroid antagonist ZK98299 prevented PR binding to 
      chromatin in vivo and reversed hypersensitivity, leading to the loss of 
      transcription factor binding. The reduction in hypersensitivity induced by 
      ZK98299 was readily reversed by treatment with the progestin R5020. The chromatin 
      organization of the promoter could be cycled between the open and closed states 
      by consecutive treatments with agonist or antagonist. The antagonist RU486 also 
      blocked activation of transcription and the assembly of a transcription 
      preinitiation complex, but in contrast to ZK98299, maintained the hypersensitive 
      chromatin state. Taken together, these results suggest that PR binding to 
      chromatin is sufficient to induce hypersensitivity to endonucleolytic cleavage. 
      Furthermore, they indicate that the PR binding to DNA and the resulting chromatin 
      hypersensitivity is functionally separate from transcriptional activation in 
      vivo.
FAU - Mymryk, J S
AU  - Mymryk JS
AD  - Department of Obstetrics and Gynaecology, University of Western Ontario, London, 
      Canada.
FAU - Archer, T K
AU  - Archer TK
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Genes Dev
JT  - Genes & development
JID - 8711660
RN  - 0 (Chromatin)
RN  - 0 (Gonanes)
RN  - 0 (Receptors, Progesterone)
RN  - 320T6RNW1F (Mifepristone)
RN  - H6H7G23O3N (onapristone)
SB  - IM
MH  - Animals
MH  - Breast Neoplasms/pathology
MH  - Cell Line, Transformed
MH  - Cell Transformation, Viral
MH  - Chromatin/drug effects/*metabolism
MH  - Female
MH  - Gonanes/pharmacology
MH  - Humans
MH  - Mammary Tumor Virus, Mouse/genetics
MH  - Mice
MH  - Mifepristone/pharmacology
MH  - Promoter Regions, Genetic/genetics
MH  - Receptors, Progesterone/antagonists & inhibitors/genetics/*metabolism
MH  - Signal Transduction
MH  - Transcriptional Activation/drug effects
EDAT- 1995/06/01 00:00
MHDA- 1995/06/01 00:01
CRDT- 1995/06/01 00:00
PHST- 1995/06/01 00:00 [pubmed]
PHST- 1995/06/01 00:01 [medline]
PHST- 1995/06/01 00:00 [entrez]
AID - 10.1101/gad.9.11.1366 [doi]
PST - ppublish
SO  - Genes Dev. 1995 Jun 1;9(11):1366-76. doi: 10.1101/gad.9.11.1366.