Different regulation of the LXRAα promoter activity by isoforms of CCAAT/enhancer-binding proteins

LXRs have recently been shown to regulate key enzymes in cholesterol degradation, reverse transport of cholesterol from peripheral cells, cholesterol uptake and lipogenesis. The LXRα promoter was thus studied to investigate if LXR gene expression is under the regulation of transcription factors involved in adipogenesis. We report that the C/EBP transcription factor interacts with the promoter of the LXR gene. In in vitro footprinting experiments, protein extracts from several tissues gave footprints covering a putative C/EBP recognition site. Transfection experiments and EMSA showed a direct effect of these transcription factors on the LXRα promoter. C/EBPα upregulated expression of the reporter gene in an NIH 3T3-L1 preadipocyte cell line, while C/EBPβ and C/EBPδ had no effect. In liver hepatoma Fao II and Cos-7 kidney cells, both C/EBPα and C/EBPβ downregulated expression of the reporter gene while C/EBPδ induced activity, indicating that the functional consequences of C/EBP isoform interactions with the LXRα promoter are dependent on the cellular context. Monitoring of the LXR mRNA levels during adipose tissue differentiation showed that LXRβ is constitutively expressed during the entire differentiation process while LXRα is induced upon addition of differentiation mix.