A Global Role for EKLF in Definitive and Primitive Erythropoiesis

摘要: Erythroid Kruppel-like factor (EKLF, KLF1) plays an important role in definitive erythropoiesis and β-globin gene regulation but failure to rectify lethal fetal anemia upon correction of globin chain imbalance suggested additional critical EKLF target genes. We employed expression profiling EKLF-null liver erythroid cell lines containing inducible EKLF-estrogen receptor (EKLF-ER) fusion construct search for such targets. An overlapping list EKLF-regulated genes from the 2 systems included α-hemoglobin stabilizing protein (AHSP), cytoskeletal proteins, hemesynthesis enzymes, transcription factors, blood group antigens. One gene, dematin, which encodes erythrocyte (band 4.9), contains several phylogenetically conserved consensus CACC motifs predicted bind EKLF. Chromatin immunoprecipitation demonstrated vivo occupancy at these sites promoter reporter assays showed that activates through DNA elements. Furthermore, investigation yolk sac led discovery unexpected defects embryonic red membrane cytoskeleton. In short, regulates global is development primitive cells.