PMID- 11278601
OWN - NLM
STAT- MEDLINE
DCOM- 20010705
LR  - 20210209
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 276
IP  - 20
DP  - 2001 May 18
TI  - Transcriptional repression by thyroid hormone receptors. A role for receptor 
      homodimers in the recruitment of SMRT corepressor.
PG  - 16857-67
AB  - Nuclear hormone receptors, such as the thyroid hormone receptors (T3Rs) and 
      retinoid X receptors (RXRs), are ligand-regulated transcription factors that 
      control key aspects of metazoan gene expression. T3Rs can bind to DNA either as 
      receptor homodimers or as heterodimers with RXRs. Once bound to DNA, nuclear 
      hormone receptors regulate target gene expression by recruiting auxiliary 
      proteins, denoted corepressors and coactivators. We report here that T3R 
      homodimers assembled on DNA exhibit particularly strong interactions with the 
      SMRT corepressor, whereas T3R.RXR heterodimers are inefficient at binding to 
      SMRT. Mutants of T3R that exhibit enhanced repression properties, such as the 
      v-Erb A oncoprotein or the T3Rbeta-Delta432 mutant found in human resistance to 
      thyroid hormone syndrome, display enhanced homodimerization properties and 
      exhibit unusually strong interactions with the SMRT corepressor. Significantly, 
      the topology of a DNA binding site can determine whether that site recruits 
      primarily homodimers or heterodimers and therefore whether corepressor is 
      efficiently or inefficiently recruited to the resulting receptor-DNA complex. We 
      suggest that T3R homodimers, and not heterodimers, may be important mediators of 
      transcriptional repression and that the nature of the DNA binding site, by 
      selecting for receptor homodimers or heterodimers, can influence the ability of 
      the receptor to recruit corepressor.
FAU - Yoh, S M
AU  - Yoh SM
AD  - Section of Microbiology, Division of Biological Sciences, University of 
      California, Davis, California 95616, USA.
FAU - Privalsky, M L
AU  - Privalsky ML
LA  - eng
GR  - R01 DK-53528/DK/NIDDK NIH HHS/United States
GR  - R01 DK-54064/DK/NIDDK NIH HHS/United States
GR  - R37 CA-53394/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
DEP - 20010221
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (NCOR2 protein, human)
RN  - 0 (Nuclear Receptor Co-Repressor 2)
RN  - 0 (Oncogene Proteins v-erbA)
RN  - 0 (Receptors, Retinoic Acid)
RN  - 0 (Receptors, Thyroid Hormone)
RN  - 0 (Recombinant Proteins)
RN  - 0 (Repressor Proteins)
RN  - 0 (Retinoid X Receptors)
RN  - 0 (Transcription Factors)
RN  - 06LU7C9H1V (Triiodothyronine)
SB  - IM
MH  - Animals
MH  - Cell Line
MH  - Cloning, Molecular
MH  - DNA-Binding Proteins/*metabolism
MH  - Dimerization
MH  - *Gene Expression Regulation/drug effects
MH  - Genes, erbA
MH  - Humans
MH  - Mutation
MH  - Nuclear Receptor Co-Repressor 2
MH  - Oncogene Proteins v-erbA/*genetics
MH  - Receptors, Retinoic Acid/metabolism
MH  - Receptors, Thyroid Hormone/chemistry/*metabolism
MH  - Recombinant Proteins/chemistry/metabolism
MH  - Repressor Proteins/chemistry/*metabolism
MH  - Retinoid X Receptors
MH  - Transcription Factors/metabolism
MH  - *Transcription, Genetic
MH  - Transfection
MH  - Triiodothyronine/pharmacology
EDAT- 2001/03/30 10:00
MHDA- 2001/07/06 10:01
CRDT- 2001/03/30 10:00
PHST- 2001/03/30 10:00 [pubmed]
PHST- 2001/07/06 10:01 [medline]
PHST- 2001/03/30 10:00 [entrez]
AID - S0021-9258(19)31856-3 [pii]
AID - 10.1074/jbc.M010022200 [doi]
PST - ppublish
SO  - J Biol Chem. 2001 May 18;276(20):16857-67. doi: 10.1074/jbc.M010022200. Epub 2001 
      Feb 21.