PMID- 9140065
OWN - NLM
STAT- MEDLINE
DCOM- 19970806
LR  - 20191102
IS  - 1356-9597 (Print)
IS  - 1356-9597 (Linking)
VI  - 1
IP  - 2
DP  - 1996 Feb
TI  - Inhibition of ligand induced promoter occupancy in vivo by a dominant negative 
      RXR.
PG  - 209-21
AB  - BACKGROUND: Retinoid X receptors (RXRs) heterodimerize with other nuclear hormone 
      receptors and control ligand mediated transcription. To address how RXRs function 
      as heterodimers, we investigated activities of truncated RXR alpha and RXR beta 
      that lack approximately 20 conserved C-terminal amino acids. RESULTS: The 
      truncated RXRs formed heterodimers and bound to respective DNA elements in vitro. 
      By transient reporter assays we found that these RXRs act as dominant negative 
      receptors and inhibit ligand dependent transcription by the retinoic acid 
      receptor (RAR) and vitamin D receptor. P19 embryonal carcinoma cells stably 
      expressing the truncated RXR beta (termed delta C2) were deficient in activating 
      the endogenous RAR beta gene and an RA responsive reporter. To study the dominant 
      negative activity of delta C2 further, genomic footprinting analysis was 
      performed for the RAR beta2 promoter. In control P19 clones, the RA responsive 
      element (RARE) and other elements in the promoter were protected after RA 
      treatment. However, in delta C2 clones RA-induced protection was markedly 
      inhibited at all elements. CONCLUSIONS: These results indicate that the 
      C-terminal region of RXR is required for full RARE occupancy in vivo, a RA 
      dependent process that leads to the recruitment of other factors to the promoter 
      and the subsequent transcriptional activation. Thus, RXRs play an integral role 
      in ligand dependent transcription.
FAU - Blanco, J C
AU  - Blanco JC
AD  - Laboratory of Molecular Growth Regulation, National Institute of Child Health and 
      Human Development, National Institutes of Health, Bethesda, MD 20892, USA.
FAU - Dey, A
AU  - Dey A
FAU - Leid, M
AU  - Leid M
FAU - Minucci, S
AU  - Minucci S
FAU - Park, B K
AU  - Park BK
FAU - Jurutka, P W
AU  - Jurutka PW
FAU - Haussler, M R
AU  - Haussler MR
FAU - Ozato, K
AU  - Ozato K
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - England
TA  - Genes Cells
JT  - Genes to cells : devoted to molecular & cellular mechanisms
JID - 9607379
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Ligands)
RN  - 0 (Receptors, Calcitriol)
RN  - 0 (Receptors, Retinoic Acid)
RN  - 0 (Retinoid X Receptors)
RN  - 0 (Transcription Factors)
RN  - 1406-16-2 (Vitamin D)
RN  - 5688UTC01R (Tretinoin)
SB  - IM
MH  - Animals
MH  - DNA Footprinting
MH  - DNA Methylation
MH  - DNA-Binding Proteins/*genetics
MH  - Gene Expression Regulation
MH  - Genes, Reporter
MH  - Ligands
MH  - Mice
MH  - Models, Genetic
MH  - *Promoter Regions, Genetic
MH  - Protein Binding
MH  - Receptors, Calcitriol
MH  - Receptors, Retinoic Acid/*genetics
MH  - Retinoid X Receptors
MH  - Sequence Deletion
MH  - Transcription Factors/*genetics
MH  - Transcription, Genetic
MH  - Tretinoin/metabolism
MH  - Tumor Cells, Cultured
MH  - Vitamin D/metabolism
EDAT- 1996/02/01 00:00
MHDA- 1996/02/01 00:01
CRDT- 1996/02/01 00:00
PHST- 1996/02/01 00:00 [pubmed]
PHST- 1996/02/01 00:01 [medline]
PHST- 1996/02/01 00:00 [entrez]
AID - 10.1046/j.1365-2443.1996.d01-229.x [doi]
PST - ppublish
SO  - Genes Cells. 1996 Feb;1(2):209-21. doi: 10.1046/j.1365-2443.1996.d01-229.x.