PMID- 8119995
OWN - NLM
STAT- MEDLINE
DCOM- 19940404
LR  - 20210210
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 269
IP  - 9
DP  - 1994 Mar 4
TI  - Thyroid hormone receptor functions as monomeric ligand-induced transcription 
      factor on octameric half-sites. Consequences also for dimerization.
PG  - 6444-9
AB  - The thyroid hormone (3,5,3'-triiodothyronine) receptor (T3R) belongs to the 
      nuclear receptor superfamily of ligand-inducible transcription factors. T3Rs are 
      known to bind as homodimers and heterodimers with retinoid X receptors (RXRs) to 
      two hexameric half-sites in directly repeated, palindromic, and inverted 
      palindromic orientations. The binding of T3R monomers to individual half-sites 
      was often reported, but no clear ligand-induced transactivational activity has 
      been shown. Here, we analyzed interactions of T3R monomers with individual 
      half-sites of the sequence NNAGGTCA. We found that the two nucleotides 5' of the 
      AGGTCA core half-site strongly influence T3R binding and transcriptional 
      activity: octameric half-sites of the consensus sequence (T/C)(A/G)AGGTCA were 
      bound by T3Rs with the highest affinity. This suggests T3R functioning also as a 
      monomeric transcription factor like the orphan nuclear receptors NGFI-B and 
      FTZ-F1. Moreover, we observed that the function of T3R-RXR heterodimers on 
      response elements composed of two half-sites in a directly repeated orientation 
      spaced by 4 nucleotides is determined in major parts by the 5'-flanking sequence 
      of the upstream half-site. Consequently, we noted that the affinity of T3R 
      homodimers is influenced by both 5'-flanking sequences. Our findings suggest that 
      the binding of dimerizing receptors like T3R and other nuclear receptors to their 
      cognate response elements is determined not only by the half-site core sequence, 
      orientation, and number of spacing nucleotides, but also by the nucleotide 
      sequence preceding the half-sites.
FAU - Schrader, M
AU  - Schrader M
AD  - Clinique de Dermatologie, Hopital Cantonal Universitaire, Geneve, Switzerland.
FAU - Becker-Andre, M
AU  - Becker-Andre M
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 (Ligands)
RN  - 0 (Macromolecular Substances)
RN  - 0 (Oligodeoxyribonucleotides)
RN  - 0 (Receptors, Cytoplasmic and Nuclear)
RN  - 0 (Receptors, Retinoic Acid)
RN  - 0 (Receptors, Thyroid Hormone)
RN  - 0 (Retinoid X Receptors)
RN  - 0 (Transcription Factors)
RN  - 06LU7C9H1V (Triiodothyronine)
RN  - 9007-49-2 (DNA)
RN  - EC 2.3.1.28 (Chloramphenicol O-Acetyltransferase)
SB  - IM
MH  - Animals
MH  - Base Sequence
MH  - Binding Sites
MH  - Cell Line
MH  - Chloramphenicol O-Acetyltransferase/biosynthesis/metabolism
MH  - DNA/*metabolism
MH  - Drosophila
MH  - Kinetics
MH  - Ligands
MH  - Macromolecular Substances
MH  - Molecular Sequence Data
MH  - Oligodeoxyribonucleotides
MH  - Protein Biosynthesis
MH  - Receptors, Cytoplasmic and Nuclear/biosynthesis/isolation & 
      purification/*metabolism
MH  - *Receptors, Retinoic Acid
MH  - Receptors, Thyroid Hormone/biosynthesis/isolation & purification/*metabolism
MH  - Retinoid X Receptors
MH  - Transcription Factors/biosynthesis/isolation & purification/*metabolism
MH  - Transfection
MH  - Triiodothyronine/*pharmacology
EDAT- 1994/03/04 00:00
MHDA- 1994/03/04 00:01
CRDT- 1994/03/04 00:00
PHST- 1994/03/04 00:00 [pubmed]
PHST- 1994/03/04 00:01 [medline]
PHST- 1994/03/04 00:00 [entrez]
AID - S0021-9258(17)37392-1 [pii]
PST - ppublish
SO  - J Biol Chem. 1994 Mar 4;269(9):6444-9.