Data/hora: 09/06/2024 02:47:30

Provedor de dados: 	Brazilian Journal of Medical and Biological Research	
País: 	Brazil	
Título: 	Influence of the polymorphisms of the α-major regulatory element HS-40 on in vitro gene expression	
Autores: 	Ribeiro,D.M.; Zaccariotto,T.R.; Santos,M.N.N.; Costa,F.F.; Sonati,M.F.	
Data: 	2009-09-01	
Ano: 	2009	
Palavras-chave: 	Alpha-major regulatory element; HS-40; Alpha-globin genes; Genetic polymorphisms; Gene expression.	
Resumo: 	The α-MRE is the major regulatory element responsible for the expression of human α-like globin genes. It is genetically polymorphic, and six different haplotypes, named A to F, have been identified in some population groups from Europe, Africa and Asia and in native Indians from two Brazilian Indian tribes. Most of the mutations that constitute the α-MRE haplotypes are located in flanking sequences of binding sites for nuclear factors. To our knowledge, there are no experimental studies evaluating whether such variability may influence the α-MRE enhancer activity. We analyzed and compared the expression of luciferase of nine constructs containing different α-MRE elements as enhancers. Genomic DNA samples from controls with A (wild-type α-MRE) and B haplotypes were used to generate C-F haplotypes by site-directed mutagenesis. In addition, three other elements containing only the G→A polymorphism at positions +130, +199, and +209, separately, were also tested. The different α-MRE elements were amplified and cloned into a plasmid containing the luciferase reporter gene and the SV40 promoter and used to transiently transfect K562 cells. A noticeable reduction in luciferase expression was observed with all constructs compared with the A haplotype. The greatest reductions occurred with the F haplotype (+96, C→A) and the isolated polymorphism +209, both located near the SP1 protein-binding sites believed not to be active in vivo. These are the first analyses of α-MRE polymorphisms on gene expression and demonstrate that these single nucleotide polymorphisms, although outside the binding sites for nuclear factors, are able to influence in vitro gene expression.	
Tipo: 	Info:eu-repo/semantics/other	
Idioma: 	Inglês	
Identificador: 	http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0100-879X2009000900002	
Editor: 	Associação Brasileira de Divulgação Científica	
Relação: 	10.1590/S0100-879X2009005000014	
Formato: 	text/html	
Fonte: 	Brazilian Journal of Medical and Biological Research  v.42 n.9 2009	
Fonte: 	info:eu-repo/semantics/openAccess