PMID- 8119880
OWN - NLM
STAT- MEDLINE
DCOM- 19940401
LR  - 20210210
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 269
IP  - 8
DP  - 1994 Feb 25
TI  - Specificity and flexibility of vitamin D signaling. Modulation of the activation 
      of natural vitamin D response elements by thyroid hormone.
PG  - 5501-4
AB  - Cellular responsiveness to 1,25-dihydroxyvitamin D3 (VD) is conferred by its 
      intracellular receptor (VDR), which belongs to the nuclear receptor superfamily 
      of ligand-inducible transcription factors. VDRs are known to bind to specific 
      response elements in the promoter region of VD-regulated genes. Two types of 
      natural VD response elements (VDREs) have been identified so far. One is bound by 
      VDR homodimers and is found in the human osteocalcin gene promoter (DR6-type), 
      and the other is bound by heterodimers of VDR with retinoid X receptors (RXRs) as 
      in the mouse osteopontin promoter (DR3-type). Here, we demonstrate that VDRs 
      directly interact in solution not only with RXR but also with retinoid acid 
      receptors (RARs) and, interestingly, with thyroid hormone receptors (T3Rs). All 
      three heterodimeric partners were able to enhance the in vitro DNA binding 
      affinity of VDR as compared to VDR homodimers, but they showed different 
      affinities for the two types of VDREs, as determined by Scatchard analysis. 
      Moreover, functional assays showed that VDR.T3R heterodimers act differently on 
      the two types of VDREs; on the DR3-type we observed highest induction by thyroid 
      hormone (3,5,3'-triiodothyronine, T3) alone, whereas on a DR6-type VDRE VD and T3 
      together provided maximal gene activity. Our data suggest that the expression 
      levels of VDRs, RXRs, RARs, and T3Rs and their specific ligands regulate the 
      transcription of VD-responsive genes and illustrates the complexity of this 
      interactive network of nuclear receptors.
FAU - Schrader, M
AU  - Schrader M
AD  - Clinique de Dermatologie, Hopital Cantonal Universitaire, Geneve, Switzerland.
FAU - Muller, K M
AU  - Muller KM
FAU - Carlberg, C
AU  - Carlberg C
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Receptors, Cytoplasmic and Nuclear)
RN  - 0 (Receptors, Retinoic Acid)
RN  - 0 (Receptors, Thyroid Hormone)
RN  - 0 (Retinoid X Receptors)
RN  - 0 (Thyroid Hormones)
RN  - 0 (Transcription Factors)
RN  - 1406-16-2 (Vitamin D)
RN  - 9007-49-2 (DNA)
SB  - IM
MH  - Animals
MH  - Base Sequence
MH  - Binding Sites
MH  - Cells, Cultured
MH  - DNA/metabolism
MH  - Drosophila
MH  - Humans
MH  - Molecular Sequence Data
MH  - Receptors, Cytoplasmic and Nuclear/metabolism
MH  - Receptors, Retinoic Acid/metabolism
MH  - Receptors, Thyroid Hormone/metabolism
MH  - Retinoid X Receptors
MH  - *Signal Transduction
MH  - Thyroid Hormones/*pharmacology
MH  - *Transcription Factors
MH  - Vitamin D/*metabolism
EDAT- 1994/02/25 00:00
MHDA- 1994/02/25 00:01
CRDT- 1994/02/25 00:00
PHST- 1994/02/25 00:00 [pubmed]
PHST- 1994/02/25 00:01 [medline]
PHST- 1994/02/25 00:00 [entrez]
AID - S0021-9258(17)37487-2 [pii]
PST - ppublish
SO  - J Biol Chem. 1994 Feb 25;269(8):5501-4.