Nuclear orphan receptors regulate transcription of the gene for the human luteinizing hormone receptor.
J Biol Chem
; 275(4): 2763-70, 2000 Jan 28.
Article
em En
| MEDLINE
| ID: mdl-10644740
ABSTRACT
An imperfect estrogen receptor half-site response element direct-repeat, located within the TATA-less promoter of the human luteinizing hormone receptor (hLHR), was identified as an inhibitory site for Sp1/Sp3-driven basal transcription. Isolation of proteins recognizing this site by yeast one-hybrid screening of a human placenta cDNA library revealed three nuclear orphan receptors, EAR2, EAR3/COUP-TFI, and TR4. Electrophoresis mobility shift assays demonstrated that the in vitro translated nuclear orphan receptors specifically bound the direct-repeat motif of the hLHR promoter. Also, endogenous EAR2 and EAR3/COUP-TFI from JAR cell and human testis and TR4 from testes bound this motif in electrophoresis mobility shift assays. Functional analyses in CV-1 cells showed that EAR2 and EAR3/COUP-TFI repressed the hLHR promoter activity by up to 70% in a dose-dependent and sequence-specific manner. Conversely, TR4 activated the hLHR promoter activity up to 2.5-fold through binding to the same cis-element. The stimulation was reversed by coexpression of EAR2 or EAR3/COUP-TFI, indicating their competitive binding for this site. Such recognition of a common cognate site by the proteins with antagonistic functions implies that a net regulation of the hLHR gene may result from the relative availability of repressors and activator in a physiological state. This also may contribute to the differential expression of the hLHR gene in gonadal and non-gonadal tissues.
Buscar no Google
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Fatores de Transcrição
/
Transcrição Gênica
/
Receptores do LH
/
Receptores dos Hormônios Tireóideos
/
Receptores de Esteroides
/
Proteínas de Ligação a DNA
/
Proteínas do Tecido Nervoso
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Revista:
J Biol Chem
Ano de publicação:
2000
Tipo de documento:
Article
País de afiliação:
Estados Unidos