Molecular analysis of the human fetal-to-adult globin switching.
Southeast Asian J Trop Med Public Health
;
1995 ; 26 Suppl 1(): 212-20
Artículo
en Inglés
| IMSEAR
| ID: sea-30860
ABSTRACT
Hereditary persistence of fetal hemoglobin (HPFH) is a condition characterized by continued expression of the gamma-globin gene in adult life. Analysis of a Japanese HPFH family had revealed that the C-T transition at position -114 within the distal CCAAT box of the gamma-globin gene associated with the HPFH allele. In the vicinity of the distal CCAAT box, other two mutations (-117 C-T, 13 bp del) had been identified in individuals with a HPFH phenotype. Functional analysis of these mutant promoters in erythroid cell lines suggested that the distal CCAAT box works positively in the fetus but negatively in the adult on the expression of the gamma-globin gene. Further study on transgenic mice showed that the -114 mutation was responsible for the elevated expression of the gamma-globin gene in the adult. To elucidate the molecular mechanism underlying the persistent expression of the gamma-globin genes associated with the HPFH mutations, interaction of the mutant promoters with nuclear factors was analyzed. Relevance of the nuclear factor, NFE3, to the gamma-globin regulation was suggested by the affected binding of NFE3 to the altered distal CCAAT boxes with HPFH mutations (-117, -114, 13 bp del).
Texto completo:
Disponible
Índice:
IMSEAR (Asia Sudoriental)
Asunto principal:
Oligodesoxirribonucleótidos
/
Fenotipo
/
Sitios de Unión
/
Humanos
/
Hemoglobina Fetal
/
Globinas
/
Hemoglobina A
/
Ratones Transgénicos
/
Datos de Secuencia Molecular
/
Células Tumorales Cultivadas
Tipo de estudio:
Estudio pronóstico
País/Región como asunto:
Asia
Idioma:
Inglés
Revista:
Southeast Asian J Trop Med Public Health
Año:
1995
Tipo del documento:
Artículo
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