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. In the present study, chicken homologues of the human KLF2, 3, 4, 5, 9, 11, 12, 13, and 15 genes were identified. Phylogenetic analysis confirms that these genes are more closely related to their human homologues than they are to other chicken KLFs. This work also represents the first systematic study of the expression patterns of KLFs during erythroid development. In addition, transient transfections of human globin constructs into 5-day (primitive) chicken red blood cells show that human gamma-globin expression is regulated via its CACCC promoter element. This indicates that a CACCC-binding factor(s) important for gamma-globin expression functions in 5-day chicken red cells.