Expression of the human endogenous retrovirus (HERV) group HML-2/HERV-K does not depend on canonical promoter elements but is regulated by transcription factors Sp1 and Sp3.
J Virol
; 85(7): 3436-48, 2011 Apr.
Article
em En
| MEDLINE
| ID: mdl-21248046
ABSTRACT
After fixation in the human genome, human endogenous retroviruses (HERVs) are bona fide cellular genes despite their exogenous origin. To be able to spread within the germ line and the early embryo, the ancient retroviral promoters must have adapted to the requirements for expression in these cell types. We describe that in contrast to the case for current exogenous retroviruses, which replicate in specific somatic cells, the long terminal repeat (LTR) of the human endogenous retrovirus HERV-K acts as a TATA- and initiator element-independent promoter with a variable transcription start site. We present evidence that the HERV-K LTR is regulated by the transcription factors Sp1 and Sp3. Mutating specific GC boxes, which are binding sites for Sp proteins, and knocking down Sp1 and Sp3 by use of small interfering RNA (siRNA) significantly reduced the promoter activity. Binding of Sp1 and Sp3 to the promoter region was confirmed using electrophoretic mobility shift assays (EMSAs) and chromatin immunoprecipitation (ChIP). Our data explain why certain HERV-K proviruses have lost promoter competence. Since vertebrate promoters lacking canonical core promoter elements are common but poorly studied, understanding the HERV-K promoter not only will provide insight into the regulation of endogenous retroviruses but also can serve as a paradigm for understanding the regulation of this class of cellular genes.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Fator de Transcrição Sp1
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Regiões Promotoras Genéticas
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Retrovirus Endógenos
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Sequências Repetidas Terminais
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Fator de Transcrição Sp3
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Interações Hospedeiro-Patógeno
Limite:
Humans
Idioma:
En
Revista:
J Virol
Ano de publicação:
2011
Tipo de documento:
Article
País de afiliação:
Alemanha