| First Author | Degagné E | Year | 2012 |
| Journal | FEBS J | Volume | 279 |
| Issue | 16 | Pages | 2957-65 |
| PubMed ID | 22742194 | Mgi Jnum | J:201030 |
| Mgi Id | MGI:5510655 | Doi | 10.1111/j.1742-4658.2012.08676.x |
| Citation | Degagne E, et al. (2012) P2Y(2) receptor expression is regulated by C/EBPbeta during inflammation in intestinal epithelial cells. FEBS J 279(16):2957-65 |
| abstractText | Inflammatory bowel diseases are characterized by relapses and remission periods during which numerous factors, including stress factors and nucleotides, are mobilized to re-establish intestinal mucosal homeostasis. We have previously found that expression of the P2Y(2) nucleotide receptor is increased in colonic tissue isolated from inflammatory bowel disease patients as well as in a mouse model of colitis, and that P2Y(2) transcription is regulated in part by nuclear factor kappaB (NF-kappaB) p65. Transcription factor DNA-binding site analysis identified three potential CCAAT/enhancer-binding protein beta (C/EBPbeta) binding sites in the P2Y(2) proximal promoter. We then assessed the role of C/EBP transcription factors in the regulation of P2Y(2) in intestinal epithelial cells (IECs). We identified a region between -229 and -220 bp upstream of the transcription initiation site as a DNA-binding site for C/EBPbeta, by electrophoretic mobility and supershift assays. Mutagenesis of this site decreased C/EBPbeta-dependent P2Y(2) expression, as assessed by luciferase assays. In vivo, C/EBPbeta as well as P2Y(2) expression was increased in colonic IECs isolated from mice with dextran sulfate sodium-induced acute colitis. In contrast, P2Y(2) expression was decreased in C/EBPbeta-deficient mice treated with dextran sulfate sodium. Although C/EBPbeta was sufficient to induce P2Y(2) transcription, the effect of C/EBPbeta and NF-kappaB p65 on receptor transcription was synergistic. Chromatin immunoprecipitation assays revealed that both proteins simultaneously bind to the P2Y(2) promoter. Thus, we have identified C/EBPbeta as a novel regulator of P2Y(2) expression. |
