Regulation of cdc2 gene expression by the upstream stimulatory factors (USFs)

cdc2 gene expression is under the control of multiple factors. Although E2F/DP proteins have been reported to play a central role, they cannot account for all aspects of the fine modulation of cdc2 gene expression during cell cycle and embryonic development. To characterize the transcription factors that control cdc2 gene expression during nerve cell differentiation in avians, we have previously cloned the quail cdc2 gene promoter region. We had identified an octamer (CAGGTGGC) containing an E-box, which has important activity in regulating cdc2 transcription. Using in vivo genomic footprinting experiments, we show here that this motif, currently named IG, is the target of binding proteins at different stages of neuroretina development, confirming its importance as a regulatory response element for cdc2 gene expression. A subset of Helix-Loop-Helix family of transcription factors, known as Upstream Stimulatory Factors (USFs) specifically bind to this sequence as dimers. Moreover, our results indicate that USFs transactivate the promoter of cdc2 via the IG motif. These data may help to better understand the mechanisms that control cell division in differentiating nerve cells.