A core SMRT corepressor complex containing HDAC3 and TBL1, a WD40-repeat protein linked to deafness.

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.
Authors	M G Guenther, W S Lane, W Fischle, E Verdin, M A Lazar, R Shiekhattar
Journal	Genes & development (Genes Dev) Vol. 14 Issue 9 Pg. 1048-57 (May 01 2000) ISSN: 0890-9369 [Print] United States
PMID	10809664 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
Chemical References	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
Topics	Amino Acid Sequence Animals Basic Helix-Loop-Helix Transcription Factors Cell Line Chromatography, Affinity DNA-Binding Proteins (chemistry, genetics, metabolism) Fungal Proteins (chemistry) HeLa Cells Hearing Loss, Sensorineural (genetics) Histone Deacetylases (chemistry, genetics, metabolism) Humans Mice Molecular Sequence Data Nuclear Proteins Nuclear Receptor Co-Repressor 2 Peptide Fragments (chemistry, immunology) Recombinant Proteins (chemistry, metabolism) Repetitive Sequences, Amino Acid Repressor Proteins (chemistry, genetics, metabolism) Saccharomyces cerevisiae Proteins Transducin (chemistry, genetics, metabolism) Transfection

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