EcR interacts with corepressors and harbours an autonomous silencing domain functional in both Drosophila and vertebrate cells.
The ecdysone receptor (EcR) is a member of the large family of nuclear hormone receptors, which are ligand regulated transcription factors. In general, ligand converts these receptors into a transcriptional activator. Some vertebrate nuclear hormone receptors, such as the thyroid hormone and retinoic acid receptors, silence gene expression in the absence of ligand. EcR is involved in fly metamorphosis and is used in vertebrates as an inducible system for expression of transgenes. Here, we show that a Drosophila receptor, the EcR, harbours an autonomous silencing function in its carboxy-terminus. Interestingly, EcR mediates also silencing in vertebrate cells. In concordance with this EcR interacts with the corepressors SMRT and N-CoR, while addition of ligand reduces this interaction. Conversely, the v-erbA oncogene product, a thyroid hormone receptor derivative, mediates silencing in Drosophila cells. Thus, our data suggest the involvement of an evolutionarily conserved mechanism by which nuclear hormone receptors mediate gene silencing in multicellular organisms.
Thormeyer
D
D
Genetisches Institut der Justus-Liebig-Universität, Giessen, Germany.
Tenbaum
S P
SP
Renkawitz
R
R
Baniahmad
A
A
D000818:Animals; D002460:Cell Line; D002522:Chlorocebus aethiops; D004268:DNA-Binding Proteins; D004331:Drosophila melanogaster / Q000166:cytology / Q000502:physiology*; D004441:Ecdysterone / Q000031:analogs & derivatives* / Q000494:pharmacology; D005656:Fungal Proteins / Q000096:biosynthesis / Q000235:genetics; D005786:Gene Expression Regulation / Q000187:drug effects; D018160:Receptors, Cytoplasmic and Nuclear / Q000737:chemistry / Q000502:physiology; D011987:Receptors, Steroid / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis; D011994:Recombinant Proteins / Q000378:metabolism; D012097:Repressor Proteins / Q000378:metabolism*; D012441:Saccharomyces cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors / Q000096:biosynthesis / Q000235:genetics; D014162:Transfection
D004268:DNA-Binding Proteins; D005656:Fungal Proteins; C052130:GAL4 protein, S cerevisiae; D018160:Receptors, Cytoplasmic and Nuclear; D011987:Receptors, Steroid; D011993:Recombinant Fusion Proteins; D011994:Recombinant Proteins; D012097:Repressor Proteins; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors; C055469:ecdysone receptor; C055348:muristerone A; D004441:Ecdysterone