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Title

The specificity protein factor Sp1 mediates transcriptional regulation of P2X7 receptors in the nervous system

AuthorsGarcía-Huerta, Paula; Díaz-Hernández, Miguel; Delicado, Esmerilda G.; Pimentel-Santillana, María ; Miras-Portugal, María Teresa; Gómez-Villafuertes, Rosa
Issue Date2012
PublisherAmerican Society for Biochemistry and Molecular Biology
CitationJournal of Biological Chemistry 287(53): 44628-44644 (2012)
AbstractP2X7 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 abouthowexpression 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. © 2012 by The American Society for Biochemistry and Molecular Biology, Inc.
URIhttp://hdl.handle.net/10261/78033
DOI10.1074/jbc.M112.390971
Identifiersdoi: 10.1074/jbc.M112.390971
issn: 0021-9258
e-issn: 1083-351X
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