Differential binding of the NFE3 and CP1/NFY transcription factors to the human gamma- and epsilon-globin CCAAT boxes.
J Biol Chem
; 270(37): 21934-41, 1995 Sep 15.
Article
in En
| MEDLINE
| ID: mdl-7545172
ABSTRACT
Naturally occurring nondeletional mutations affecting the distal CCAAT box of the human gamma-globin gene promoter result in hereditary persistence of fetal hemoglobin in adult life. Although the distal CCAAT box is the target of several factors, including CP1/NFY, CDP, GATA-1 and NFE3, only NFE3 binding activity is consistently sensitive to well characterized mutations in this region such as G-117-->A, C-114-->T, and delta 13 hereditary persistence of fetal hemoglobin. We extensively characterized the binding specificities of NFE3 and demonstrated that NFE3 has unique properties with respect to other CCAAT box-binding proteins. Affinity-purified NFE3 from erythroid K562 cells binds the distal but not the proximal human gamma-globin CCAAT box, the single CCAAT box of the human epsilon-globin promoter, and the proximal CCAAT box of the evolutionarily related Galago crassicaudatus gamma-globin gene. Within the epsilon-globin CCAAT box, NFE3 represents the major and almost exclusive binding activity. Disruption of such a binding site essentially inactivates the epsilon-globin promoter, suggesting that NFE3 plays an important role in the embryonic expression of this gene.
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Collection:
01-internacional
Database:
MEDLINE
Main subject:
Transcription Factors
/
Globins
/
Fungal Proteins
/
Nuclear Proteins
/
Promoter Regions, Genetic
/
CCAAT-Enhancer-Binding Proteins
/
Saccharomyces cerevisiae Proteins
/
DNA-Binding Proteins
Limits:
Adult
/
Humans
Language:
En
Journal:
J Biol Chem
Year:
1995
Document type:
Article
Affiliation country:
Italy