Abstract
The corepressor SMRT mediates repression by thyroid hormone receptor (TR) as well as other nuclear hormone receptors and transcription factors. Here we report the isolation of a novel SMRT-containing complex from HeLa cells. This complex contains transducin beta-like protein 1 (TBL1), whose gene is mutated in human sensorineural deafness. It also contains HDAC3, a histone deacetylase not previously thought to interact with SMRT. TBL1 displays structural and functional similarities to Tup1 and Groucho corepressors, sharing their ability to interact with histone H3. In vivo, TBL1 is bridged to HDAC3 through SMRT and can potentiate repression by TR. Intriguingly, loss-of-function TRbeta mutations cause deafness in mice and humans. These results define a new TR corepressor complex with a physical link to histone structure and a potential biological link to deafness.
Publication types
-
Research Support, Non-U.S. Gov't
-
Research Support, U.S. Gov't, P.H.S.
MeSH terms
-
Amino Acid Sequence
-
Animals
-
Basic Helix-Loop-Helix Transcription Factors
-
Cell Line
-
Chromatography, Affinity
-
DNA-Binding Proteins / chemistry
-
DNA-Binding Proteins / genetics
-
DNA-Binding Proteins / metabolism*
-
Fungal Proteins / chemistry
-
HeLa Cells
-
Hearing Loss, Sensorineural / genetics*
-
Histone Deacetylases / chemistry
-
Histone Deacetylases / genetics
-
Histone Deacetylases / metabolism*
-
Humans
-
Mice
-
Molecular Sequence Data
-
Nuclear Proteins*
-
Nuclear Receptor Co-Repressor 2
-
Peptide Fragments / chemistry
-
Peptide Fragments / immunology
-
Recombinant Proteins / chemistry
-
Recombinant Proteins / metabolism
-
Repetitive Sequences, Amino Acid
-
Repressor Proteins / chemistry
-
Repressor Proteins / genetics
-
Repressor Proteins / metabolism*
-
Saccharomyces cerevisiae Proteins*
-
Transducin / chemistry
-
Transducin / genetics*
-
Transducin / metabolism*
-
Transfection
Substances
-
Basic Helix-Loop-Helix Transcription Factors
-
DNA-Binding Proteins
-
Fungal Proteins
-
NCOR2 protein, human
-
Ncor2 protein, mouse
-
Nuclear Proteins
-
Nuclear Receptor Co-Repressor 2
-
Peptide Fragments
-
Recombinant Proteins
-
Repressor Proteins
-
Saccharomyces cerevisiae Proteins
-
TBL1X protein, human
-
TUP1 protein, S cerevisiae
-
Tbl1x protein, mouse
-
gro protein, Drosophila
-
Histone Deacetylases
-
histone deacetylase 3
-
Transducin