Synergistic activation of the chicken mim‐1 gene by v‐myb and C/EBP transcription factors

The retroviral oncogene v‐myb encodes a transcriptional activator which is responsible for the activation of the mim‐1 gene in myelomonocytic cells transformed by v‐myb. The mim‐1 promoter contains several myb consensus binding sites and has previously been shown to be regulated directly by v‐myb. Here we report that the mim‐1 gene is activated synergistically by v‐myb and different C/EBP transcription factors. We have cloned a chicken C/EBP‐related gene that is highly expressed in myeloid cells and identified it as the chicken homolog of C/EBP beta. A dominant‐negative variant of chicken C/EBP beta interferes with the v‐myb induced activation of the mim‐1 gene in these cells, suggesting that C/EBP beta or another C/EBP transcription factor is required for the activation of mim‐1 by v‐myb. We found that C/EBP beta and other C/EBP transcription factors confer to fibroblasts the ability to induce the mim‐1 gene in the presence of v‐myb. Finally we show that, in contrast to v‐myb, c‐myb synergizes with C/EBP transcription factors only at low concentrations of c‐myb protein. Our results suggest a role for C/EBP beta, and possibly for other C/EBP transcription factors, in v‐myb function and in myeloid‐specific gene activation.