PMID- 7626514
OWN - NLM
STAT- MEDLINE
DCOM- 19950907
LR  - 20190830
IS  - 0960-0760 (Print)
IS  - 0960-0760 (Linking)
VI  - 53
IP  - 1-6
DP  - 1995 Jun
TI  - Receptor mediated genomic action of the 1,25(OH)2D3 hormone: expression of the 
      human vitamin D receptor in E. coli.
PG  - 583-94
AB  - The nuclear vitamin D receptor (VDR) binds the 1,25-dihydroxyvitamin D3 
      (1,25(OH)2D3) hormone with high affinity and elicits its actions to stimulate 
      gene expression in target cells by binding to the vitamin D-responsive element 
      (VDRE). VDREs in such positively controlled genes as osteocalcin, osteopontin, 
      beta 3 integrin and vitamin D-24-OHase are direct hexanucleotide repeats with a 
      spacer of three nucleotides. The present studies of VDR/VDRE interaction utilized 
      full-length human vitamin D receptor (hVDR) that was overexpressed in E. coli, 
      purified to near homogeneity (> 95%), and its authenticity confirmed by 
      demonstrating high affinity hormone binding and reactivity to monoclonal antibody 
      9A7 gamma. The expressed hVDR displays strict dependence on the family of 
      retinoid X receptors (RXRs) for binding to the vitamin D-responsive element 
      (VDRE) in the rat osteocalcin gene. Similar overexpression in E. coli of the DNA 
      binding domain (delta 134), containing only residues 4-133 of hVDR, generated a 
      receptor species that possesses intrinsic DNA binding activity. Both full-length 
      and delta 134 hVDRs retain similar DNA binding specificities when tested with 
      several natural hormone responsive elements, indicating that the N-terminal zinc 
      finger region determines hVDR-DNA sequence selectivity. The C-terminal region of 
      the molecule is required for hormone binding and confers the receptor with the 
      property of very high affinity DNA binding, via heterodimerization between hVDR 
      and RXR. A natural ligand for the RXR co-receptor, 9-cis retinoic acid, 
      suppresses both VDR-RXR binding to the VDRE and 1,25(OH)2D3 stimulated 
      transcription, indicating that 9-cis retinoic acid recruits RXR away from VDR to 
      instead form RXR homodimers.
FAU - Hsieh, J C
AU  - Hsieh JC
AD  - Department of Biochemistry, College of Medicine, University of Arizona, Tucson 
      85724, USA.
FAU - Nakajima, S
AU  - Nakajima S
FAU - Galligan, M A
AU  - Galligan MA
FAU - Jurutka, P W
AU  - Jurutka PW
FAU - Haussler, C A
AU  - Haussler CA
FAU - Whitfield, G K
AU  - Whitfield GK
FAU - Haussler, M R
AU  - Haussler MR
LA  - eng
GR  - AR15781/AR/NIAMS NIH HHS/United States
GR  - DK33351/DK/NIDDK NIH HHS/United States
GR  - DK40372/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - England
TA  - J Steroid Biochem Mol Biol
JT  - The Journal of steroid biochemistry and molecular biology
JID - 9015483
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Oligodeoxyribonucleotides)
RN  - 0 (Receptors, Calcitriol)
RN  - 0 (Recombinant Proteins)
RN  - FXC9231JVH (Calcitriol)
SB  - IM
GS  - VDR
MH  - Base Sequence
MH  - Calcitriol/*physiology
MH  - Cloning, Molecular
MH  - DNA-Binding Proteins/chemistry/genetics
MH  - Escherichia coli
MH  - Humans
MH  - In Vitro Techniques
MH  - Molecular Sequence Data
MH  - Oligodeoxyribonucleotides/chemistry
MH  - Receptors, Calcitriol/chemistry/*genetics
MH  - Recombinant Proteins
MH  - Regulatory Sequences, Nucleic Acid
MH  - Structure-Activity Relationship
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 - 0960-0760(95)00112-D [pii]
AID - 10.1016/0960-0760(95)00112-d [doi]
PST - ppublish
SO  - J Steroid Biochem Mol Biol. 1995 Jun;53(1-6):583-94. doi: 
      10.1016/0960-0760(95)00112-d.