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

Abstract

The Krüppel-like factors (KLFs) are a family of Cys 2His 2 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 γ -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 γ-globin expression is regulated via its CACCC promoter element. This indicates that a CACCC-binding factor(s) important for γ -globin expression functions in 5-day chicken red cells.