EKLF and KLF2 have compensatory roles in embryonic beta-globin gene expression and primitive erythropoiesis.

The Krüppel-like C2/H2 zinc finger transcription factors (KLFs) control development and differentiation. Erythroid Krüppel-like factor (EKLF or KLF1) regulates adult beta-globin gene expression and is necessary for normal definitive erythropoiesis. KLF2 is required for normal embryonic Ey- and betah1-, but not adult betaglobin, gene expression in mice.

Evolutionary conservation of KLF transcription factors and functional conservation of human gamma-globin gene regulation in chicken.

The Krüppel-like factors (KLFs) are a family of Cys2His2 zinc-finger DNA binding proteins with homology to Drosophila Krüppel. KLFs can bind to CACCC elements, which are important in controlling developmental programs. The CACCC promoter element is critical for the developmental regulation of the human gamma-globin gene.

Methylation of promoter proximal-transcribed sequences of an embryonic globin gene inhibits transcription in primary erythroid cells and promotes formation of a cell type-specific methyl cytosine binding complex.

The methylation pattern of a 248-base pair proximal transcribed region (rho248) of the avian embryonic rho-globin gene was found to correlate inversely with stage-specific expression in avian erythroid cells. In vitro methylation of the rho248 segment alone (in the absence of promoter methylation) resulted in a 5-fold inhibition of transcription in a transient transfection assay in primary erythroid cells in which the transfected gene is packaged into nucleosomal chromatin. This effect was observed if the rho248 segment was positioned adjacent to the promoter but not when it was located 2.