Transcriptional co-repressor that interacts with nuclear hormone receptors and uses therefor

A method to identify compounds which relieve the suppression of steroid/thyroid hormone receptor activity caused by a co-suppressor having a structure and function characteristic of the silencing mediator for retinoic acid and thyroid receptors, said method comprising

• determining the effect of a test compound on the level of reporter signal produced by an expression system comprising:
• (i) a modified member of the steroid/thyroid hormone superfamily of receptors, wherein said modified member contains an activation domain which renders said receptor constitutively active,
• (ii) a fusion protein comprising the receptor interaction domain of said co-suppressor operatively linked to the GAL4 DNA binding domain, wherein said co-suppressor comprises amino acid residues 1-1329 plus 1376-1495, as set forth in SEQ ID NO:1, or conservative amino acid variations thereof, wherein said co-suppressor forms a complex with at least one member of the steroid/thyroid hormone superfamily of receptors and optionally a response element for said member, thereby mediating transcriptional silencing, wherein said transcriptional silencing is relieved in the presence of a ligand for said member of the steroid/thyroid hormone superfamily of receptors, and wherein said receptor interaction domain comprises the C-terminal domain of said co-suppressor, and
• (iii) a GAL4 response element operatively linked to a reporter gene,
• wherein a decrease in the reporter signal in the presence of said test compound is indicative of a compound that relieves the suppression of said receptor activity.