REGULATION OF E2F-1 GENE-EXPRESSION IN AVIAN CELLS

E2F-1 is the prototype of a family of transcription factors playing a central role in the control of cell proliferation and apoptosis, E2F D NA binding activity is down-regulated during cellular differentiation, which is correlated with cell division arrest. We report here that th e expression of E2F-1 itself is down-regulated in the developing quail neural retina between embryonic days E8-E10, This event occurs just a fter the massive arrest of the quail neuroretina cell division (E7-E8) , To gain further insight into the regulatory mechanisms monitoring E2 F-1 expression in differentiating neurons, we have cloned the quail E2 F-1 promoter. In vivo DNA footprintings of this promoter have shown th at a number of potential SP-1 and C/EBP response elements are constitu tively occupied in the entire quail neuroretina of E5 and E14, whereas the two consensus palindromic E2F binding sites are only protected at E5, This suggests that these E2F elements participate in down-regulat ion of E2F-1 gene expression during avian neuroretina development. CAT reporter assays have shown that E2F-1 in association with its partner DP-1 transactivates its own promoter, whereas p105(Rb) inhibits the E 2F-1 promoter. Both E2F-1/DP-1 and pl05(Rb) require the presence of th e E2F binding sites to mediate their effects. However, experiments per formed with deletion mutants of the promoter strongly suggest that oth er regions located upstream of the E2F binding sites also mediate part of the E2F-1 transactivating effect on its own promoter. Altogether, these results suggest that the down-regulation of E2F-1 gene expressio n in differentiating neurons could be due, in part, to the E2F/Rb comp lexes binding to the E2F-1 promoter.