Cloning and Transcriptional Activity Analysis of the Porcine Abcb1 Gene Promoter: Transcription Factor Sp1 Regulates the Expression of Porcine Abcb1
P-Glycoprotein (P-gp, Abcb1) plays a crucial role in drug disposition and functions by hydrolyzing ATP. However, little is known about the regulatory elements governing the transcription of the porcine Abcb1 gene. In this study, the transcription start site of the pig Abcb1 gene was identified by 5′...
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Frontiers Media S.A.
2018-05-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | http://journal.frontiersin.org/article/10.3389/fphar.2018.00373/full |
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| author | Tingting Guo Tingting Guo Jinhu Huang Changchao Huan Fang He Yujuan Zhang Zohaib A. Bhutto Liping Wang |
| author_facet | Tingting Guo Tingting Guo Jinhu Huang Changchao Huan Fang He Yujuan Zhang Zohaib A. Bhutto Liping Wang |
| author_sort | Tingting Guo |
| collection | DOAJ |
| description | P-Glycoprotein (P-gp, Abcb1) plays a crucial role in drug disposition and functions by hydrolyzing ATP. However, little is known about the regulatory elements governing the transcription of the porcine Abcb1 gene. In this study, the transcription start site of the pig Abcb1 gene was identified by 5′-RACE. A 1.9-kb fragment of the 5′-flanking region of the Abcb1 gene was cloned from pig genomic DNA and sequenced. The region critical for its promoter activity was investigated via progressive deletions. Further, using mutation assays, two proximal Sp1 binding sites within the 5′-flanking region of Abcb1 were proven to be important cis-regulatory elements involved in regulating the constitutive expression of porcine Abcb1. RNA interference experiments showed that Sp1 regulated the expression of the porcine P-gp at both mRNA and protein levels. Hence, the current work provides valuable information on the regulatory mechanisms of pig Abcb1. |
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| id | doaj.art-9a8434e5c29e49db8d66fc1a414b91e5 |
| institution | Directory Open Access Journal |
| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-04-13T07:06:56Z |
| publishDate | 2018-05-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Pharmacology |
| spelling | doaj.art-9a8434e5c29e49db8d66fc1a414b91e52022-12-22T02:56:59ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122018-05-01910.3389/fphar.2018.00373327567Cloning and Transcriptional Activity Analysis of the Porcine Abcb1 Gene Promoter: Transcription Factor Sp1 Regulates the Expression of Porcine Abcb1Tingting Guo0Tingting Guo1Jinhu Huang2Changchao Huan3Fang He4Yujuan Zhang5Zohaib A. Bhutto6Liping Wang7Laboratory of Veterinary Pharmacology and Toxicology, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, ChinaMedical College, Yangzhou University, Yangzhou, ChinaLaboratory of Veterinary Pharmacology and Toxicology, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, ChinaCollege of Veterinary Medicine, Yangzhou University, Yangzhou, ChinaLaboratory of Veterinary Pharmacology and Toxicology, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, ChinaLaboratory of Veterinary Pharmacology and Toxicology, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, ChinaLaboratory of Veterinary Pharmacology and Toxicology, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, ChinaLaboratory of Veterinary Pharmacology and Toxicology, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, ChinaP-Glycoprotein (P-gp, Abcb1) plays a crucial role in drug disposition and functions by hydrolyzing ATP. However, little is known about the regulatory elements governing the transcription of the porcine Abcb1 gene. In this study, the transcription start site of the pig Abcb1 gene was identified by 5′-RACE. A 1.9-kb fragment of the 5′-flanking region of the Abcb1 gene was cloned from pig genomic DNA and sequenced. The region critical for its promoter activity was investigated via progressive deletions. Further, using mutation assays, two proximal Sp1 binding sites within the 5′-flanking region of Abcb1 were proven to be important cis-regulatory elements involved in regulating the constitutive expression of porcine Abcb1. RNA interference experiments showed that Sp1 regulated the expression of the porcine P-gp at both mRNA and protein levels. Hence, the current work provides valuable information on the regulatory mechanisms of pig Abcb1.http://journal.frontiersin.org/article/10.3389/fphar.2018.00373/fullAbcb1promotertranscription factorregulationSp1porcine |
| spellingShingle | Tingting Guo Tingting Guo Jinhu Huang Changchao Huan Fang He Yujuan Zhang Zohaib A. Bhutto Liping Wang Cloning and Transcriptional Activity Analysis of the Porcine Abcb1 Gene Promoter: Transcription Factor Sp1 Regulates the Expression of Porcine Abcb1 Frontiers in Pharmacology Abcb1 promoter transcription factor regulation Sp1 porcine |
| title | Cloning and Transcriptional Activity Analysis of the Porcine Abcb1 Gene Promoter: Transcription Factor Sp1 Regulates the Expression of Porcine Abcb1 |
| title_full | Cloning and Transcriptional Activity Analysis of the Porcine Abcb1 Gene Promoter: Transcription Factor Sp1 Regulates the Expression of Porcine Abcb1 |
| title_fullStr | Cloning and Transcriptional Activity Analysis of the Porcine Abcb1 Gene Promoter: Transcription Factor Sp1 Regulates the Expression of Porcine Abcb1 |
| title_full_unstemmed | Cloning and Transcriptional Activity Analysis of the Porcine Abcb1 Gene Promoter: Transcription Factor Sp1 Regulates the Expression of Porcine Abcb1 |
| title_short | Cloning and Transcriptional Activity Analysis of the Porcine Abcb1 Gene Promoter: Transcription Factor Sp1 Regulates the Expression of Porcine Abcb1 |
| title_sort | cloning and transcriptional activity analysis of the porcine abcb1 gene promoter transcription factor sp1 regulates the expression of porcine abcb1 |
| topic | Abcb1 promoter transcription factor regulation Sp1 porcine |
| url | http://journal.frontiersin.org/article/10.3389/fphar.2018.00373/full |
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