PMID- 17311926
OWN - NLM
STAT- MEDLINE
DCOM- 20070614
LR  - 20210209
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 282
IP  - 17
DP  - 2007 Apr 27
TI  - Thyroid hormone response element organization dictates the composition of active 
      receptor.
PG  - 12458-66
AB  - Thyroid hormone (triiodothyronine, T(3)) is known to activate transcription by 
      binding heterodimers of thyroid hormone receptors (TRs) and retinoid X receptors 
      (RXRs). RXR-TRs bind to T(3) response elements (TREs) composed of direct repeats 
      of the sequence AGGTCA spaced by four nucleotides (DR-4). In other TREs, however, 
      the half-sites can be arranged as inverted palindromes and palindromes (Pal). 
      Here we show that TR homodimers and monomers activate transcription from 
      representative TREs with alternate half-site placements. TR beta activates 
      transcription more efficiently than TR alpha at an inverted palindrome (F2), and 
      this correlates with preferential TR beta homodimer formation at F2 in vitro. 
      Furthermore, reconstruction of TR transcription complexes in yeast indicates that 
      TR beta homodimers are active at F2, whereas RXR-TRs are active at DR-4 and Pal. 
      Finally, analysis of TR beta mutations that block homodimer and/or heterodimer 
      formation reveal TRE-selective requirements for these surfaces in mammalian 
      cells, which suggest that TR beta homodimers are active at F2, RXR-TRs at DR-4, 
      and TR monomers at Pal. TR beta requires higher levels of hormone for activation 
      at F2 than other TREs, and this differential effect is abolished by a dimer 
      surface mutation suggesting that it is related to composition of the TR.TRE 
      complex. We propose that interactions of particular TR oligomers with different 
      elements play unappreciated roles in TRE-selective actions of liganded TRs in 
      vivo.
FAU - Velasco, Lara F R
AU  - Velasco LF
AD  - Molecular Pharmacology Laboratory, Department of Pharmaceutical Sciences, School 
      of Health Sciences, University of Brasilia, Brasilia, DF, Brazil.
FAU - Togashi, Marie
AU  - Togashi M
FAU - Walfish, Paul G
AU  - Walfish PG
FAU - Pessanha, Rutineia P
AU  - Pessanha RP
FAU - Moura, Fanny N
AU  - Moura FN
FAU - Barra, Gustavo B
AU  - Barra GB
FAU - Nguyen, Phuong
AU  - Nguyen P
FAU - Rebong, Rachelle
AU  - Rebong R
FAU - Yuan, Chaoshen
AU  - Yuan C
FAU - Simeoni, Luiz A
AU  - Simeoni LA
FAU - Ribeiro, Ralff C J
AU  - Ribeiro RC
FAU - Baxter, John D
AU  - Baxter JD
FAU - Webb, Paul
AU  - Webb P
FAU - Neves, Francisco A R
AU  - Neves FA
LA  - eng
GR  - DK41482/DK/NIDDK NIH HHS/United States
GR  - DK51281/DK/NIDDK NIH HHS/United States
GR  - DK61468/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20070220
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Retinoid X Receptors)
RN  - 0 (Thyroid Hormone Receptors alpha)
RN  - 0 (Thyroid Hormone Receptors beta)
RN  - 06LU7C9H1V (Triiodothyronine)
SB  - IM
MH  - Dimerization
MH  - HeLa Cells
MH  - Humans
MH  - Mutation
MH  - *Response Elements
MH  - Retinoid X Receptors/metabolism
MH  - Thyroid Hormone Receptors alpha/agonists/genetics/*metabolism
MH  - Thyroid Hormone Receptors beta/agonists/genetics/*metabolism
MH  - Transcription, Genetic/drug effects/*physiology
MH  - Triiodothyronine/metabolism/*pharmacology
MH  - U937 Cells
EDAT- 2007/02/22 09:00
MHDA- 2007/06/15 09:00
CRDT- 2007/02/22 09:00
PHST- 2007/02/22 09:00 [pubmed]
PHST- 2007/06/15 09:00 [medline]
PHST- 2007/02/22 09:00 [entrez]
AID - S0021-9258(18)95018-0 [pii]
AID - 10.1074/jbc.M610700200 [doi]
PST - ppublish
SO  - J Biol Chem. 2007 Apr 27;282(17):12458-66. doi: 10.1074/jbc.M610700200. Epub 2007 
      Feb 20.