Characterization of a novel quiescence responsive element downregulated byv-Src in the promoter of the neuroretina specific QR1 gene

The neuroretina is a functional unit of the central nervous system which ar ises through successive steps of division, growth arrest and differentiatio n of neuroectodermal precursors. Postmitotic quail neuroretina (QNR) cells are conditionally induced to divide upon infection with temperature sensiti ve mutants of Rous sarcoma virus (RSV), since QNR cell division can be arre sted by either inactivating p60v-Src at the nonpermissive temperature (41 d egrees C) or by serum deprivation at 37 degrees C. We are studying the tran scriptional control of QR1, a neuroretina specific gene, whose expression i s down-regulated in proliferating cells at 37 degrees C and is fully restor ed when these cells are made quiescent. We previously showed that this quie scence specific upregulation implicates a promoter region named A box, whic h binds Maf transcription factors. We report the identification of the C bo x, a second promoter sequence that activates QR1 transcription in non divid ing cells. This sequence is able to form two DNA-protein complexes, one of which (C4) is predominantly detected in growth arrested NR cells. We identi fied the DNA binding site for C4 and described mutations that abolish both C4 binding and promoter activity in quiescent cells. Moreover, we show that a multimerized C box is able to stimulate a heterologous promoter in non d ividing cells and constitutes, therefore, a novel quiescence responsive enh ancer. Finally, me report that QR1 transcriptional response to cell quiesce nce requires cooperation between the C box and A box.