The v-Myb oncoprotein activates C/EBPβ expression by stimulating an autoregulatory loop at the C/EBPβ promoter

Previous studies have implicated the CCAAT box/enhancer binding protein beta (C/EBP beta) in the regulation of cell-type specific gene expression in myelomonocytic cells and in the activation of target genes by the transcription factor v-Myb. To better understand the role of C/EBP beta in myelomonocytic cells we have cloned the chicken C/EBP beta gene and studied its regulation. The chicken C/EBP beta promoter contains a number of C/EBP binding sites and is activated by C/EBP beta, suggesting that the C/EBP beta gene is autoregulated by its own protein product. Interestingly, the C/EBP beta promoter is not activated by C/EBP alpha, another C/EBP family member highly expressed in myelomonocytic cells, indicating that the autoregulation is specific for C/EBP beta. Comparison of different C/EBP inducible promoters shows that the relative transactivation potential of C/EBP alpha and beta is extremely dependent on the promoter context. By using the promoters of the mim-1 and C/EBP beta genes and by exchanging the DNA-binding domains between C/EBP alpha and beta we show that the observed promoter preferences of C/EBP alpha and beta are not due to differential DNA-binding but instead depend on the transactivation domains of these proteins. The C/EBP beta promoter also contains several Myb binding motifs, suggesting that the C/EBP beta gene is also myb-inducible. We show that the C/EBP beta promoter is activated synergistically by v-Myb and C/EBP beta and that transcription of the endogenous C/EBP beta gene is increased by v-Myb. Thus, our results identify the C/EBP beta gene as a novel v-Myb target gene. Taken together, our data suggest a model for the regulation of C/EBP beta expression in which v-Myb stimulates the synthesis of C/EBP beta by enhancing an autoregulatory loop acting on the C/EBP beta promoter. (C) 1999 Elsevier Science B.V. All rights reserved.