Regulation of the human HBA genes by KLF4 in erythroid cell lines.
Br J Haematol
; 149(5): 748-58, 2010 Jun.
Article
en En
| MEDLINE
| ID: mdl-20331458
ABSTRACT
KLF1/EKLF and related Krueppel-like factors (KLFs) are variably implicated in the regulation of the HBB-like globin genes. Prompted by the observation that four KLF sites are distributed in the human alpha-globin gene (HBA) promoter, we investigated if KLFs could also act to modulate the expression of the HBA genes. Among the KLFs tested, only KLF4/GKLF bound specifically to three out of four alpha-globin KLF sites. The occupancy of the same sites by KLF4 in vivo was confirmed by chromatin immunoprecipitation assays with KLF4-specific antibodies. In luciferase reporter assays in MEL cells, high levels of the wild type HBA promoter, but not mutated promoters bearing point mutations that disrupted KLF4-DNA binding, were transactivated by over-expression of KLF4. In K562 cells, induced KLF4 expression with a Tet-off regulated cassette stimulated the expression of the endogenous HBA genes. In a complementary assay in the same cell line, knocking down KLF4 with lentiviral delivered sh-RNAs caused a parallel decrease in the transcription of the HBA genes. All experiments combined support a regulatory role of KLF4 in the control of HBA gene expression.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Hemoglobina A
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Regulación de la Expresión Génica
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Células Eritroides
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Factores de Transcripción de Tipo Kruppel
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Br J Haematol
Año:
2010
Tipo del documento:
Article
País de afiliación:
Italia