2 DISTINCT REGULATORY ELEMENTS CONTROL QUAIL CDC2 TRANSCRIPTION - POSSIBLE INVOLVEMENT IN THE CONTROL OF RETINOBLAST DIFFERENTIATION

It is a characteristic of the central nervous system of higher eukaryo tes that neurons, after an initial proliferation phase, remain postmit otic for their whale life span. In the developing quail neuroretina, m ost retinoblasts become postmitotic after 7-8 days of incubation. They also cease to express cdc2, which is presumably necessary to allow re tinoblasts to definitively leave the cell cycle. The molecular mechani sms monitoring cdc2 expression during differentiation remain partly un derstood. To further study the control of cdc2 transcription in avian cells, we have cloned the quail cdc2 promoter. Two functional regulato ry elements have been characterized, One of them contains an E2F-bindi ng site, Human E2F-1 was found to transactivate the quail cdc2 promote r very efficiently in avian and human cells, Gel retardation experimen ts are presented, suggesting that E2F, in association with different p artners, is a major regulator of cdc2 transcription during the develop ment of the neuroretina. Our data also indicate that another transcrip tion factor binds to the octamer CAGGTGGC located 115 nucleotides abov e the main transcription start site. This motif is thus another import ant regulatory element participating in the control of cdc2 expression .