The Ovine CCAAT-Enhancer Binding Protein δ Gene: Cloning, Characterization, and Species-Specific Autoregulation

Abstract

Transcription factors belonging to the CCAAT-enhancer binding protein (C/EBP) family have been implicated in the regulation of gene expression during growth, differentiation, apoptosis, and inflammation. Autoregulation is relatively common in the modulation of C/EBP gene expression and, for the human and murine C/EBPα, it is known that species-specific autoregulatory mechanisms operate. It is therefore essential to investigate the autoregulation of additional C/EBP genes from a wider range of different species to gauge the degree of commonality, or otherwise, which exists. As an important step towards this goal, we report here the cloning and the characterisation of the ovine C/EBPδ gene (ovC/EBPδ) and analysis of its promoter region. Transient transfection assays reveal that ovC/EBPδ acts as a transcriptional activator. Although several motifs that are characteristic of C/EBPδ genes are conserved in the ovine sequence, including the basic region, leucine zipper, and activation domains, two regions have been identified that are specifically absent in the ovine and bovine homologues. The ovC/EBPδ promoter is active in both the hepatoma Hep3B and the mammary epithelial HC11 cell lines, induced by the cytokine interleukin-6 and autoregulated by mechanisms that are potentially different from those described for the rat promoter. These results suggest that, in common with C/EBPα, the C/EBPδ genes may also be subject to autoregulation by distinct species-specific mechanisms.