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

The corepressor SMRT mediates repression by thyroid hormone receptor (TR) a s well as other nuclear hormone receptors and transcription factors. sere w e 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 str uctural and functional similarities to Tup1 and Groucho corepressors, shari ng their ability to interact with histone H3. In vivo, TBL1 is bridged to H DAC3 through SMRT and can potentiate repression by TR. Intriguingly, loss-o f-function TR beta mutations cause deafness in mice and humans. These resul ts define a new TR corepressor complex with a physical link to histone stru cture and a potential biological link to deafness.