Identification of a genomic DNA sequence that quantitatively modulates KLF1 expression in differentiating human hematopoietic cells

Abstract

Expression of the {beta}-like globin genes is under strict developmental control, with both direct and indirect inputs responsible for this effect. One of the major players regulating their transition is KLF1/EKLF, where even a two-fold difference in its level alters the regulation of globin switching. We have reproduced this change in KLF1 expression in both cell lines and primary human cells, thus demonstrating that directed, quantitative control of KLF1 expression can be attained by genomic manipulation, and suggest a new way in which modulation of transcription factor levels may be used for clinical benefit.