Chromatin organization plays a fundamental role in regulating transcription in eukaryotic cells. The nuclear receptor corepressor (N-CoR) and silencing mediator of retinoid and thyroid hormone receptors (SMRT) play a role in diverse transcriptional repression pathways. N-CoR and SMRT each exist in large protein complexes, and are thoμght to mediate repression, at least in part, by their ability to recruit histone deacetylases (HDAC) to generate repressive chromatin. HDAC3 is the main HDAC that associates with N-CoR and SMRT complexes and its presence is thoμght to be essential for repression. TBLR1 is a WD-40 repeat protein that also associates with N-CoR and SMRT complexes. Althoμgh TBLR1 is thoμght to be a core component of both the N-CoR and SMRT complexes, its role in these complexes remains to be elucidated.