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The distal β ‐globin CACCC box is required for maximal stimulation of the β ‐globin gene by EKLF
Author(s) -
Marini Maria Giuseppina,
Asunis Isadora,
Porcu Loredana,
Salgo Maria Giulia,
Loi Maria Giuseppina,
Brucchietti Arianna,
Cao Antonio,
Moi Paolo
Publication year - 2004
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/j.1365-2141.2004.05153.x
Subject(s) - transcription factor , globin , biology , gene , microbiology and biotechnology , mutant , genetics
Summary The transcription factor erythroid Kruppel‐like factor (EKLF) specifically activates the β ‐globin gene by interacting with the proximal β ‐globin CACCC box, a known hot spot for thalassaemia mutations. This study investigated whether EKLF could also bind to, and activate from, the distal CACCC, which is a rare site of thalassaemia mutations. Using band shift and transient expression analysis with wild type, single and double CACCC mutants, we established that the distal CACCC box is weakly bound by EKLF, but, when mutated, significantly impairs EKLF‐dependent β ‐globin stimulation. Thus, EKLF requires both CACCC boxes to maximally stimulate the β ‐globin gene.