Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 1 de 1
Filtrar
Mais filtros

Base de dados
Assunto principal
Ano de publicação
Tipo de documento
País de afiliação
Intervalo de ano de publicação
1.
J Biol Chem ; 279(21): 21793-801, 2004 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-14970235

RESUMO

The human alpha-globin complex lies at the tip of the short arm of chromosome 16. It comprises three functional globin genes (5'-zeta2-alpha2-alpha1-3'), the expression of which is strictly dependent on a positive regulatory element located 40-kb upstream, HS-40. This DNase I-hypersensitive site is the only known regulatory element displaying strong erythroid-specific enhancer activity within the human alpha-globin complex. How this enhancer activity is shared among different erythroid genes present in the same cluster without affecting the ubiquitous genes present within and around the complex is poorly understood. To address this issue, we used hybrid murine erythroleukemia cells containing a single copy of human chromosome 16 and targeted the insertion of different sequences downstream of HS-40 by recombinase-mediated cassette exchange. We thus demonstrate that (i). HS-40-mediated erythroid-specific activation of the alpha-globin genes is impaired solely by the insertion of a promoter sequence and not a coding sequence, unless it is methylated, and that (ii). the degree of transcriptional repression observed seems to be related directly to the transcriptional rate of the inserted promoter. Taken together, these results emphasize the importance of promoter sequences as the main targets for the activation mechanism of the human alpha-globin genes by HS-40.


Assuntos
Globinas/química , Animais , Sítios de Ligação , Linhagem Celular Tumoral , Cromossomos Humanos Par 16 , Clonagem Molecular , Genes Reguladores , Globinas/metabolismo , Humanos , Camundongos , Modelos Genéticos , Mutagênese , Plasmídeos/metabolismo , Regiões Promotoras Genéticas , Recombinases/metabolismo , Ribonucleases/metabolismo , Transcrição Gênica
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA