biostudies-literatureUnknown284(31)Tallack MRDifferentiation of erythroid cells requires precise control over the cell cycle to regulate the balance between cell proliferation and differentiation. The zinc finger transcription factor, erythroid Krüppel-like factor (EKLF/KLF1), is essential for proper erythroid cell differentiation and regulates many erythroid genes. Here we show that loss of EKLF leads to aberrant entry into S-phase of the cell cycle during both primitive and definitive erythropoiesis. This cell cycle defect was associated with a significant reduction in the expression levels of E2f2 and E2f4, key factors necessary for the induction of S-phase gene expression and erythropoiesis. We found and validated novel intronic enhancers in both the E2f2 and E2f4 genes, which contain conserved CACC, GATA, and E-BOX elements. TheThe Journal of biological chemistry20966-74https://www.ebi.ac.uk/biostudies/studies/S-EPMC2742862biostudies-literatureEKLF/KLF1 controls cell cycle entry via direct regulation of E2f2.PMC2742862Perkins ACTallack MRHumbert POKeys JRfalseEKLF/KLF1 controls cell cycle entry via direct regulation of E2f2.Differentiation of erythroid cells requires precise control over the cell cycle to regulate the balance between cell proliferation and differentiation. The zinc finger transcription factor, erythroid Krüppel-like factor (EKLF/KLF1), is essential for proper erythroid cell differentiation and regulates many erythroid genes. Here we show that loss of EKLF leads to aberrant entry into S-phase of the cell cycle during both primitive and definitive erythropoiesis. This cell cycle defect was associated with a significant reduction in the expression levels of E2f2 and E2f4, key factors necessary for the induction of S-phase gene expression and erythropoiesis. We found and validated novel intronic enhancers in both the E2f2 and E2f4 genes, which contain conserved CACC, GATA, and E-BOX elements. The2009-01-01T00:00:00Z2009 Jul2025-04-20T01:54:29.548Z2019-03-27T00:24:55ZS-EPMC27428621945785910.1074/jbc.m109.00634610.1074/jbc.M109.006346