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The Specificity Protein Factor Sp1 Mediates Transcriptional Regulation of P2X7 Receptors in the Nervous System
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 g...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Society for Biochemistry and Molecular Biology
2012
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3531778/ https://www.ncbi.nlm.nih.gov/pubmed/23139414 http://dx.doi.org/10.1074/jbc.M112.390971 |
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author | García-Huerta, Paula Díaz-Hernandez, Miguel Delicado, Esmerilda G. Pimentel-Santillana, María Miras-Portugal, Mª Teresa Gómez-Villafuertes, Rosa |
author_facet | García-Huerta, Paula Díaz-Hernandez, Miguel Delicado, Esmerilda G. Pimentel-Santillana, María Miras-Portugal, Mª Teresa Gómez-Villafuertes, Rosa |
author_sort | García-Huerta, Paula |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-3531778 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | American Society for Biochemistry and Molecular Biology |
record_format | MEDLINE/PubMed |
spelling | pubmed-35317782012-12-28 The Specificity Protein Factor Sp1 Mediates Transcriptional Regulation of P2X7 Receptors in the Nervous System García-Huerta, Paula Díaz-Hernandez, Miguel Delicado, Esmerilda G. Pimentel-Santillana, María Miras-Portugal, Mª Teresa Gómez-Villafuertes, Rosa J Biol Chem Neurobiology 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. American Society for Biochemistry and Molecular Biology 2012-12-28 2012-11-08 /pmc/articles/PMC3531778/ /pubmed/23139414 http://dx.doi.org/10.1074/jbc.M112.390971 Text en © 2012 by The American Society for Biochemistry and Molecular Biology, Inc. Author's Choice—Final version full access. Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) applies to Author Choice Articles |
spellingShingle | Neurobiology García-Huerta, Paula Díaz-Hernandez, Miguel Delicado, Esmerilda G. Pimentel-Santillana, María Miras-Portugal, Mª Teresa Gómez-Villafuertes, Rosa The Specificity Protein Factor Sp1 Mediates Transcriptional Regulation of P2X7 Receptors in the Nervous System |
title | The Specificity Protein Factor Sp1 Mediates Transcriptional Regulation of P2X7 Receptors in the Nervous System |
title_full | The Specificity Protein Factor Sp1 Mediates Transcriptional Regulation of P2X7 Receptors in the Nervous System |
title_fullStr | The Specificity Protein Factor Sp1 Mediates Transcriptional Regulation of P2X7 Receptors in the Nervous System |
title_full_unstemmed | The Specificity Protein Factor Sp1 Mediates Transcriptional Regulation of P2X7 Receptors in the Nervous System |
title_short | The Specificity Protein Factor Sp1 Mediates Transcriptional Regulation of P2X7 Receptors in the Nervous System |
title_sort | specificity protein factor sp1 mediates transcriptional regulation of p2x7 receptors in the nervous system |
topic | Neurobiology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3531778/ https://www.ncbi.nlm.nih.gov/pubmed/23139414 http://dx.doi.org/10.1074/jbc.M112.390971 |
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