| First Author | Tallack MR | Year | 2009 |
| Journal | J Biol Chem | Volume | 284 |
| Issue | 31 | Pages | 20966-74 |
| PubMed ID | 19457859 | Mgi Jnum | J:153105 |
| Mgi Id | MGI:4360863 | Doi | 10.1074/jbc.M109.006346 |
| Citation | Tallack MR, et al. (2009) EKLF/KLF1 controls cell cycle entry via direct regulation of E2f2. J Biol Chem 284(31):20966-74 |
| abstractText | 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 Kruppel-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. The E2f2 enhancer was occupied by EKLF in vivo. Furthermore, we were able to partially restore cell cycle dynamics in EKLF(-/-) fetal liver upon additional genetic depletion of Rb, establishing a genetic causal link between reduced E2f2 and the EKLF cell cycle defect. Finally, we propose direct regulation of the E2f2 enhancer is a generic mechanism by which many KLFs regulate proliferation and differentiation. |
