PMID- 7862171
OWN - NLM
STAT- MEDLINE
DCOM- 19950323
LR  - 20210526
IS  - 0270-7306 (Print)
IS  - 1098-5549 (Electronic)
IS  - 0270-7306 (Linking)
VI  - 15
IP  - 3
DP  - 1995 Mar
TI  - The ligand-binding domains of the thyroid hormone/retinoid receptor gene 
      subfamily function in vivo to mediate heterodimerization, gene silencing, and 
      transactivation.
PG  - 1817-25
AB  - The ligand-binding domains (LBDs) of the thyroid/retinoid receptor gene subfamily 
      contain a series of heptad motifs important for dimeric interactions. This 
      subfamily includes thyroid hormone receptors (T3Rs), all-trans retinoic acid (RA) 
      receptors (RARs), 9-cis RA receptors (RARs and retinoid X receptors [RXRs]), the 
      1,25-dihydroxyvitamin D3 receptor (VDR), and the receptors that modulate the 
      peroxisomal beta-oxidation pathway (PPARs). These receptors bind to their DNA 
      response elements in vitro as heterodimers with the RXRs. Unliganded receptors in 
      vivo, in particular the T3Rs, can mediate gene silencing and ligand converts 
      these receptors into a transcriptionally active form. The in vivo interactions of 
      these receptors with RXR were studied by using a GAL4-RXR chimera containing the 
      yeast GAL4 DNA-binding domain and the LBD of RXR beta. GAL4-RXR activates 
      transcription from GAL4 response elements in the presence of 9-cis RA. Unliganded 
      T3R, which does not bind or activate GAL4 elements, represses the activation of 
      GAL4-RXR by 9-cis RA in HeLa cells. However, addition of T3 alone leads to 
      transcriptional activation. These findings suggest that T3R can repress or 
      activate transcription while tethered to the LBD of GAL4-RXR and that 
      heterodimerization can occur in vivo without stabilization by hormone response 
      elements. Similar ligand-dependent activation was observed in HeLa cells 
      expressing RAR, VDR, or PPAR and in GH4C1 cells from endogenous receptors. 
      Replacement of the last 17 amino acids of the LBD of RXRbeta with the 
      90-amino-acid transactivating domain of the herpes simplex virus VP16 protein 
      leads to a GAL4 constitutive activator that is repressed by wild-type T3R but not 
      by a ninth heptad mutant that does not form heterodimers. This finding suggests 
      that the ninth heptad or T3R is important for gene silencing and that the LBD of 
      RXR does not exhibit silencing activity. This conclusion was verified with 
      GAL4-LBD chimeras and with wild-type receptors in assays using appropriate 
      response elements. These studies indicate that the LBD has diverse functional 
      roles in gene regulation.
FAU - Qi, J S
AU  - Qi JS
AD  - Department of Medicine, New York University Medical Center, New York 10016.
FAU - Desai-Yajnik, V
AU  - Desai-Yajnik V
FAU - Greene, M E
AU  - Greene ME
FAU - Raaka, B M
AU  - Raaka BM
FAU - Samuels, H H
AU  - Samuels HH
LA  - eng
SI  - GENBANK/L40904
GR  - DK16636/DK/NIDDK NIH HHS/United States
GR  - GM08243/GM/NIGMS NIH HHS/United States
GR  - HL07237/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Mol Cell Biol
JT  - Molecular and cellular biology
JID - 8109087
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Fungal Proteins)
RN  - 0 (GAL4 protein, S cerevisiae)
RN  - 0 (Herpes Simplex Virus Protein Vmw65)
RN  - 0 (Ligands)
RN  - 0 (RNA, Messenger)
RN  - 0 (Receptors, Calcitriol)
RN  - 0 (Receptors, Retinoic Acid)
RN  - 0 (Receptors, Thyroid Hormone)
RN  - 0 (Recombinant Fusion Proteins)
RN  - 0 (Retinoid X Receptors)
RN  - 0 (Saccharomyces cerevisiae Proteins)
RN  - 0 (Transcription Factors)
RN  - 06LU7C9H1V (Triiodothyronine)
RN  - EC 2.3.1.28 (Chloramphenicol O-Acetyltransferase)
SB  - IM
MH  - Animals
MH  - Binding Sites
MH  - Cell Line
MH  - Cells, Cultured
MH  - Chloramphenicol O-Acetyltransferase/metabolism
MH  - DNA-Binding Proteins/genetics/*metabolism
MH  - Fungal Proteins/metabolism
MH  - *Gene Expression
MH  - HeLa Cells
MH  - Herpes Simplex Virus Protein Vmw65/metabolism
MH  - Herpesvirus 1, Human/metabolism
MH  - Humans
MH  - Ligands
MH  - Molecular Sequence Data
MH  - *Multigene Family
MH  - Pituitary Gland/metabolism
MH  - Protein Multimerization
MH  - RNA, Messenger/metabolism
MH  - Rats
MH  - Receptors, Calcitriol/genetics/metabolism
MH  - Receptors, Retinoic Acid/genetics/*metabolism
MH  - Receptors, Thyroid Hormone/genetics/*metabolism
MH  - Recombinant Fusion Proteins/metabolism
MH  - Retinoid X Receptors
MH  - Saccharomyces cerevisiae/metabolism
MH  - *Saccharomyces cerevisiae Proteins
MH  - Transcription Factors/genetics/metabolism
MH  - Transcription, Genetic
MH  - *Transcriptional Activation
MH  - Transfection
MH  - Triiodothyronine/pharmacology
PMC - PMC230406
EDAT- 1995/03/01 00:00
MHDA- 1995/03/01 00:01
PMCR- 1995/03/01
CRDT- 1995/03/01 00:00
PHST- 1995/03/01 00:00 [pubmed]
PHST- 1995/03/01 00:01 [medline]
PHST- 1995/03/01 00:00 [entrez]
PHST- 1995/03/01 00:00 [pmc-release]
AID - 10.1128/MCB.15.3.1817 [doi]
PST - ppublish
SO  - Mol Cell Biol. 1995 Mar;15(3):1817-25. doi: 10.1128/MCB.15.3.1817.