| Autor: |
Ronchi, Antonella E., Bottardi, Stefania, Mazzucchelli, Cristina, Ottolenghi, Sergio, Santoro, Claudio |
| Zdroj: |
Journal of Biological Chemistry; September 1995, Vol. 270 Issue: 37 p21934-21941, 8p |
| Abstrakt: |
Naturally occurring nondeletional mutations affecting the distal CCAAT box of the human γ-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 Δ13 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 γ-globin CCAAT box, the single CCAAT box of the human ε-globin promoter, and the proximal CCAAT box of the evolutionarily related Galago crassicaudatusγ-globin gene. Within the ε-globin CCAAT box, NFE3 represents the major and almost exclusive binding activity. Disruption of such a binding site essentially inactivates the ε-globin promoter, suggesting that NFE3 plays an important role in the embryonic expression of this gene. |
| Databáze: |
Supplemental Index |
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