PMID- 8175681
OWN - NLM
STAT- MEDLINE
DCOM- 19940606
LR  - 20210210
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 269
IP  - 17
DP  - 1994 Apr 29
TI  - Half-site arrangement of hybrid glucocorticoid and thyroid hormone response 
      elements specifies thyroid hormone receptor complex binding to DNA and 
      transcriptional activity.
PG  - 12704-9
AB  - Thyroid hormone receptors bind to thyroid hormone response elements (TREs) as 
      heterodimers with 3,5,3'-L-triiodothyronine (T3) receptor auxiliary protein 
      (TRAP) and retinoid X receptors (RXRs). Currently, it is not known whether 
      TR/TRAP or TR/RXR heterodimers need to bind to both TRE half-sites and whether 
      there is a preferred orientation for TR/RXR heterodimer binding to TREs or 
      transcriptional activation. Accordingly, we created a mutant TR alpha (TR-P box) 
      by changing 3 amino acids in the P box region of the first zinc finger of the 
      DNA-binding domain to that of the glucocorticoid receptor (GR), and we examined 
      wild-type TR alpha and TR-P box complex binding to hybrid response elements 
      containing TRE and glucocorticoid receptor element (GRE) half-sites arranged as a 
      direct repeat with a four-nucleotide gap. TR-P box/RXR heterodimers selectively 
      bound to the hybrid response elements in which GRE half-site was the downstream 
      half-site, whereas TR alpha/RXR bound to hybrid response elements in which GREs 
      were in either position. Additionally, TR/TRAP or TR/RXR heterodimer required two 
      half-sites for binding to DNA, with strong binding to at least one of the 
      half-sites. Last, co-transfection assays and methylation interference studies 
      using the hybrid response elements suggest that the sequential arrangement of 
      strong and weak half-sites in the TRE may be a critical determinant of TR/RXR 
      heterodimer binding and transcriptional activation.
FAU - Yen, P M
AU  - Yen PM
AD  - Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts 
      02115.
FAU - Ikeda, M
AU  - Ikeda M
FAU - Wilcox, E C
AU  - Wilcox EC
FAU - Brubaker, J H
AU  - Brubaker JH
FAU - Spanjaard, R A
AU  - Spanjaard RA
FAU - Sugawara, A
AU  - Sugawara A
FAU - Chin, W W
AU  - Chin WW
LA  - eng
PT  - Journal Article
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Glucocorticoids)
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  - 9007-49-2 (DNA)
SB  - IM
MH  - Base Sequence
MH  - Binding Sites
MH  - Cell Line
MH  - DNA/*metabolism
MH  - DNA-Binding Proteins/metabolism
MH  - Glucocorticoids/*metabolism
MH  - Molecular Sequence Data
MH  - Receptors, Cytoplasmic and Nuclear/metabolism
MH  - *Receptors, Retinoic Acid
MH  - Receptors, Thyroid Hormone/*metabolism
MH  - *Regulatory Sequences, Nucleic Acid
MH  - Retinoid X Receptors
MH  - Thyroid Hormones/*metabolism
MH  - *Transcription Factors
MH  - *Transcription, Genetic
EDAT- 1994/04/29 00:00
MHDA- 1994/04/29 00:01
CRDT- 1994/04/29 00:00
PHST- 1994/04/29 00:00 [pubmed]
PHST- 1994/04/29 00:01 [medline]
PHST- 1994/04/29 00:00 [entrez]
AID - S0021-9258(18)99933-3 [pii]
PST - ppublish
SO  - J Biol Chem. 1994 Apr 29;269(17):12704-9.