PMID- 8825559
OWN - NLM
STAT- MEDLINE
DCOM- 19961204
LR  - 20081121
IS  - 0888-8809 (Print)
IS  - 0888-8809 (Linking)
VI  - 10
IP  - 2
DP  - 1996 Feb
TI  - Human vitamin D receptor-dependent transactivation in Saccharomyces cerevisiae 
      requires retinoid X receptor.
PG  - 196-205
AB  - Transcriptional and DNA binding activities of the human vitamin D receptor (hVDR) 
      were examined in the yeast Saccharomyces cerevisiae. In the studies described 
      here, VDR itself exhibited little transcriptional activity regardless of the 
      nature of the vitamin D-responsive elements (VDREs) used. Consistent with its 
      lack of functional activity, recombinant VDR was unable to bind to VDREs in vitro 
      using bandshift analysis. Interestingly, VDR was able to bind to VDREs with high 
      affinity and to fully activate transcription in intact yeast cells in the 
      presence of the retinoid X receptor (RXR). Although RXR subtypes displayed a 
      similar capacity to induce heterodimer formation with VDR on VDREs, RXR gamma was 
      the strongest of the subtypes in potentiating VDR-dependent transactivation. We 
      also evaluated both DNA binding and transcriptional activities of VDR alone and 
      VDR plus RXR on directly repeated response elements whose half-sites were 
      separated by three and six base pairs. DNA-binding assays together with 
      functional assays revealed that VDR was active only in the presence of RXR, 
      regardless of spacing. Using a domain-swap approach, we constructed a chimeric 
      receptor in which the DNA-binding domain of VDR was replaced with that of the 
      glucocorticoid receptor. Interaction of both wild type and chimeric receptors 
      with a hybrid-responsive element in the presence of RXR revealed that RXR and VDR 
      bound to the 5'- and 3'-half-sites of VDRE, respectively. Finally, we show that 
      the fifth position in the 3'-half-site (C) of the VDRE strongly influences the 
      binding of VDR/RXR heterodimer to its cognate cis-elements. Cumulatively, our 
      studies demonstrate, using an eukaryotic yeast system, that the functional VDR 
      unit includes RXR or an equal partner.
FAU - Jin, C H
AU  - Jin CH
AD  - Department of Skeletal Biology, Ligand Pharmaceuticals Inc., San Diego, 
      California 92121, USA.
FAU - Pike, J W
AU  - Pike JW
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Mol Endocrinol
JT  - Molecular endocrinology (Baltimore, Md.)
JID - 8801431
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Receptors, Calcitriol)
RN  - 0 (Receptors, Retinoic Acid)
RN  - 0 (Retinoid X Receptors)
RN  - 0 (Transcription Factors)
SB  - IM
MH  - Base Sequence
MH  - DNA-Binding Proteins/*genetics
MH  - Humans
MH  - Molecular Sequence Data
MH  - Receptors, Calcitriol/biosynthesis/*genetics
MH  - Receptors, Retinoic Acid/*genetics
MH  - Retinoid X Receptors
MH  - Saccharomyces cerevisiae/*genetics
MH  - Signal Transduction
MH  - Transcription Factors/*genetics
MH  - *Transcriptional Activation
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 - 10.1210/mend.10.2.8825559 [doi]
PST - ppublish
SO  - Mol Endocrinol. 1996 Feb;10(2):196-205. doi: 10.1210/mend.10.2.8825559.