RESUMO
Estrogen receptor-related receptor alpha (ERR alpha) is an orphan nuclear receptor closely related to the estrogen receptor (ER), whose expression covers various stages of embryonic development and persists in certain adult tissues. We show that ERR alpha binds as a homodimer on a specific target sequence, the SFRE (SF-1 response element), already known to respond to the orphan nuclear receptor SF-1. Target sequences that are related to the SFRE and that discriminate between ERR alpha and SF-1 were identified. We have also analyzed the transcriptional properties of the ERR alpha originating from various species. All ERR alpha orthologs act as potent transactivators through the consensus SFRE. ERR alpha activity depends on the putative AF2AD domain, as well as on a serum compound that is withdrawn by charcoal treatment, suggesting the existence of a critical regulating factor brought by serum.
Assuntos
Receptores Citoplasmáticos e Nucleares/genética , Receptores Citoplasmáticos e Nucleares/metabolismo , Receptores de Estrogênio/genética , Receptores de Estrogênio/metabolismo , Animais , Sequência de Bases , Linhagem Celular , Carvão Vegetal , Meios de Cultura , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Dimerização , Fatores de Transcrição Fushi Tarazu , Proteínas de Homeodomínio , Humanos , Camundongos , Regiões Promotoras Genéticas , Ratos , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Elementos de Resposta , Fator Esteroidogênico 1 , Transativadores/genética , Transativadores/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Transcrição Gênica , Peixe-Zebra/genética , Receptor ERRalfa Relacionado ao EstrogênioRESUMO
Estrogen receptor related alpha (ERRalpha) is an orphan nuclear receptor that is closely related to the estrogen receptor. It is expressed in a variety of adult and embryonic tissues (in particular, at the onset of ossification), as well as in several osteoblastic cell lines. ERRalpha acts as a site-specific, cell-specific transcriptional activator. Here, we show that ERRalpha transactivates the promoter of the mouse osteopontin (OPN) gene, the product of which is a marker of the late stages of osteoblastic differentiation. This effect is cell specific and is exerted through derivatives of the ERRalpha response element. Overexpression of ERRalpha in three different osteoblast-like cell lines results in an elevation of the amount of OPN-corresponding mRNA. Therefore, OPN is a target gene for ERRalpha, pointing to the role of the latter in osteoblast differentiation.
Assuntos
Osteoblastos/metabolismo , Regiões Promotoras Genéticas/genética , Receptores Citoplasmáticos e Nucleares/genética , Receptores de Estrogênio/genética , Sialoglicoproteínas/genética , Animais , Diferenciação Celular/genética , Proteínas de Ligação a DNA/genética , Estradiol/farmacologia , Fatores de Transcrição Fushi Tarazu , Regulação da Expressão Gênica/genética , Proteínas de Homeodomínio , Camundongos , Osteopontina , Mutação Puntual/genética , RNA Mensageiro/genética , Sequências Reguladoras de Ácido Nucleico/genética , Deleção de Sequência/genética , Fator Esteroidogênico 1 , Fatores de Transcrição/genética , Ativação Transcricional/genética , Transfecção/genética , Receptor ERRalfa Relacionado ao EstrogênioRESUMO
The superfamily of nuclear receptors comprises transcription factors that depend on a ligand for their activity. In addition, the superfamily includes a number of orphan receptors, for which no ligand is known. We report here that the orphan receptor estrogen receptor related alpha receptor (ERR alpha) stimulates the expression of the thyroid hormone receptor alpha (TR alpha) gene promoter. We characterized a responsive site that is both necessary and sufficient for ERR alpha-induced transactivation. In addition, we show that both TR alpha and ERR alpha are coexpressed in embryonic intestine, brown fat and heart as well as in the adult gonads. In the testis, expression of both receptors can be found in the seminiferous tubes where it is totally restricted to spermatocytes I. Altogether this suggests that TR alpha is an in vivo target of ERR alpha.