AT LEAST 3 SUBDOMAINS OF V-ERBA ARE INVOLVED IN ITS SILENCING FUNCTION

Several members of the thyroid hormone receptor (TR) family are able t o switch from a transcriptional repressor to a transcriptional activat or upon binding of their ligand. The oncogene v-erbA is a variant form of the TR unable to bind hormone and thus acts as a constitutive repr essor. We demonstrate, using fusion proteins between the DNA-binding d omain of the yeast factor GAL4 and the silencing domains of v-erbA and TR beta, that point mutations in three different regions severely aff ect their repression function. Furthermore, the three regions, each as an inactive fusion protein with the GAL4 DNA-binding domain, restore silencing activity when assembled on the same promoter. These observat ions define at least three silencing subdomains, SSD1-SSD3, which are involved in the silencing function of v-erbA. We propose a model in wh ich full silencing activity is brought about by the combined interacti on of each silencing subdomain with corepressors and/or basal transcri ption factors.