A highly conserved region in the hormone-binding domain of the human estrogen receptor functions as an efficient transactivation domain in yeast.
Human estrogen receptor (hER) mutants which activate transcription in the absence of hormone were isolated by random mutagenesis and genetic selection in the yeast Saccharomyces cerevisiae. Twenty constitutive hER mutants defining ten different alleles were selected. All sequence changes resulted in truncations of the receptor within a 123-amino-acid (aa) segment (aa 270 to 393) spanning the D region and the N-terminal part of region E which contains the hormone-binding domain (HBD). Transactivation assays using both the constitutive hER mutants and a series of deleted receptor derivatives generated in vitro revealed that the N-terminal part of region E, between aa 302 and 339, contains an efficient transcriptional activation function which is constitutively active in yeast. The location of this transactivation function in hER is similar to that of the tau 2 activation function of the glucocorticoid receptor and corresponds to a sequence which is highly conserved among the steroid hormone receptors. Thus, a conserved region exists in the HBD of the hER which can function as an autonomous transactivation domain.
Pierrat
B
B
Laboratoire de Génétique Moléculaire des Eucaryotes du CNRS, Unité 184 de l'INSERM, Institut de Chimie Biologique, Faculté de Médecine, Strasbourg, France.
Heery
D M
DM
Chambon
P
P
Losson
R
R
D000595:Amino Acid Sequence; D001665:Binding Sites / Q000502:physiology; D017124:Conserved Sequence; D017930:Genes, Reporter; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D010641:Phenotype; D011960:Receptors, Estrogen / Q000737:chemistry* / Q000235:genetics / Q000502:physiology*; D012441:Saccharomyces cerevisiae / Q000235:genetics*; D017386:Sequence Homology, Amino Acid; D015533:Transcriptional Activation / Q000502:physiology*
D011960:Receptors, Estrogen