| First Author | García-Huerta P | Year | 2012 |
| Journal | J Biol Chem | Volume | 287 |
| Issue | 53 | Pages | 44628-44 |
| PubMed ID | 23139414 | Mgi Jnum | J:250416 |
| Mgi Id | MGI:6100578 | Doi | 10.1074/jbc.M112.390971 |
| Citation | Garcia-Huerta P, et al. (2012) The specificity protein factor Sp1 mediates transcriptional regulation of P2X7 receptors in the nervous system. J Biol Chem 287(53):44628-44 |
| abstractText | P2X7 receptors are involved not only in physiological functions but also in pathological brain processes. Although an increasing number of findings indicate that altered receptor expression has a causative role in neurodegenerative diseases and cancer, little is known about how expression of P2rx7 gene is controlled. Here we reported the first molecular and functional evidence that Specificity protein 1 (Sp1) transcription factor plays a pivotal role in the transcriptional regulation of P2X7 receptor. We delimited a minimal region in the murine P2rx7 promoter containing four SP1 sites, two of them being highly conserved in mammals. The functionality of these SP1 sites was confirmed by site-directed mutagenesis and Sp1 overexpression/down-regulation in neuroblastoma cells. Inhibition of Sp1-mediated transcriptional activation by mithramycin A reduced endogenous P2X7 receptor levels in primary cultures of cortical neurons and astrocytes. Using P2rx7-EGFP transgenic mice that express enhanced green fluorescent protein under the control of P2rx7 promoter, we found a high correlation between reporter expression and Sp1 levels in the brain, demonstrating that Sp1 is a key element in the transcriptional regulation of P2X7 receptor in the nervous system. Finally, we found that Sp1 mediates P2X7 receptor up-regulation in neuroblastoma cells cultured in the absence of serum, a condition that enhances chromatin accessibility and facilitates the exposure of SP1 binding sites. |
