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 DNA binding activity is down-regulated during cellular differentiation, which is correlated with cell division arrest. We report here that the expression of E2F-1 itself is down-regulated in the developing quail neural retina between embryonic days E8-E10. This event occurs just after the massive arrest of the quail neuroretina cell division (E7-E8). To gain further insight into the regulatory mechanisms monitoring E2F-1 expression in differentiating neurons, we have cloned the quail E2F-1 promoter. In vivo DNA footprintings of this promoter have shown that a number of potential SP-1 and C/EBP response elements are constitutively 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-regulation 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 p105Rb inhibits the E2F-1 promoter. Both E2F-1/DP-1 and p105Rh require the presence of the E2F binding sites to mediate their effects. However, experiments performed with deletion mutants of the promoter strongly suggest that other 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 expression in differentiating neurons could be due, in part, to the E2F/Rb complexes binding to the E2F-1 promoter.
Espanel
X
X
Laboratoire de Biologie Moléculaire et Cellulaire, UMR 49 CNRS, ENS Lyon, France.
Le Cam
L
L
North
S
S
Sardet
C
C
Brun
G
G
Gillet
G
G
D016475:3T3 Cells; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D002478:Cells, Cultured; D018983:DNA Footprinting; D018076:DNA, Complementary; D004268:DNA-Binding Proteins; D015536:Down-Regulation; D050684:E2F Transcription Factors; D050687:E2F1 Transcription Factor; D005786:Gene Expression Regulation; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D009474:Neurons; D011401:Promoter Regions, Genetic; D011784:Quail; D012160:Retina / Q000166:cytology / Q000196:embryology; D056465:Retinoblastoma-Binding Protein 1; D050680:Transcription Factor DP1; D014157:Transcription Factors / Q000235:genetics*
C533431:Arid4a protein, mouse; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D018076:DNA, Complementary; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; D050687:E2F1 Transcription Factor; C493753:E2F1 protein, human; C493754:E2f1 protein, mouse; D056465:Retinoblastoma-Binding Protein 1; C493735:TFDP1 protein, human; C493736:Tfdp1 protein, mouse; D050680:Transcription Factor DP1; D014157:Transcription Factors