PMID- 11084025
OWN - NLM
STAT- MEDLINE
DCOM- 20010621
LR  - 20210209
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 276
IP  - 6
DP  - 2001 Feb 9
TI  - Thyroid hormone response element sequence and the recruitment of retinoid X 
      receptors for thyroid hormone responsiveness.
PG  - 3929-36
AB  - Thyroid hormone receptors (TRs) are transcription factors that bind to thyroid 
      hormone response elements (TREs) in the regulatory regions of target genes. TRs 
      are thought to activate transcription primarily as heterodimers with retinoid X 
      receptors (RXRs), with RXR binding upstream to the two directly repeated 
      half-sites in a typical TRE. However, given that TRs and RXRs prefer to bind to 
      different DNA sequences (T(A/G)AGGTCA and GGGGTCA), we postulate that only 
      certain TREs require RXR-TR heterodimerization, depending on the TRE sequence. We 
      have tested this hypothesis by comparing in Saccharomyces cerevisiae the 
      functional activity of TR +/- RXR on 10 naturally occurring mammalian TREs. S. 
      cerevisiae was used as a model system because yeast lack endogenous nuclear 
      receptors and thus can be manipulated to express TRs and/or RXRs. We first 
      studied ligand-independent reporter gene activation, which reflects the activity 
      of the activator function 1 (AF-1) domain. The 10 TREs formed a continuous 
      spectrum from being fully dependent on RXR for TR AF-1 activity to being 
      essentially independent of RXR. Relative independence of RXR generally was seen 
      when the TRE upstream half-site has a TA or TG 5' to the core hexamer. Gel 
      mobility shift assays revealed that functional independence of RXR correlates 
      with the strong binding of TR alone, whereas more RXR dependence correlates with 
      higher binding of RXR-TR heterodimers. Restoration of ligand-dependent (AF-2 
      domain) reporter gene activation was achieved by expression of the coactivator 
      TIF2. This ligand-induced stimulation was stronger in the presence of TR alone 
      than with RXR plus TR, suggesting a preference for TIF2 activation of TR 
      homodimers. Overall the data support the notion that the TRE sequence plays an 
      important role in determining the nuclear hormone receptor and coactivator 
      requirements for TR action.
FAU - Wu, Y
AU  - Wu Y
AD  - Division of Endocrinology and Metabolism, University of Michigan Medical Center, 
      Ann Arbor, Michigan 48109-0678, USA.
FAU - Xu, B
AU  - Xu B
FAU - Koenig, R J
AU  - Koenig RJ
LA  - eng
GR  - DK44155/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
DEP - 20001117
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (DNA Primers)
RN  - 0 (Receptors, Retinoic Acid)
RN  - 0 (Receptors, Thyroid Hormone)
RN  - 0 (Retinoid X Receptors)
RN  - 0 (Thyroid Hormones)
RN  - 0 (Transcription Factors)
SB  - IM
MH  - Base Sequence
MH  - DNA Primers
MH  - Dimerization
MH  - Receptors, Retinoic Acid/*metabolism
MH  - Receptors, Thyroid Hormone/*metabolism
MH  - Retinoid X Receptors
MH  - Thyroid Hormones/*metabolism
MH  - Transcription Factors/*metabolism
EDAT- 2000/11/21 00:00
MHDA- 2001/06/22 10:01
CRDT- 2000/11/21 00:00
PHST- 2000/11/21 00:00 [pubmed]
PHST- 2001/06/22 10:01 [medline]
PHST- 2000/11/21 00:00 [entrez]
AID - S0021-9258(18)46388-0 [pii]
AID - 10.1074/jbc.M006743200 [doi]
PST - ppublish
SO  - J Biol Chem. 2001 Feb 9;276(6):3929-36. doi: 10.1074/jbc.M006743200. Epub 2000 
      Nov 17.