The Enhancer Role of CYP3A4 Intron 10 in CYP3A4 Gene Expression

Wang Yi Ting; Yang Wei Hong; Zhao Yun Long; Zeng Zhao Shu; Zhang Li Rong

Article Contents

Article Navigation > Journal of Kunming Medical University > 2017 > 38(01): 13-17

Wang Yi Ting , Yang Wei Hong , Zhao Yun Long , Zeng Zhao Shu , Zhang Li Rong . The Enhancer Role of CYP3A4 Intron 10 in CYP3A4 Gene Expression[J]. Journal of Kunming Medical University, 2017, 38(01): 13-17.

Citation:

Wang Yi Ting , Yang Wei Hong , Zhao Yun Long , Zeng Zhao Shu , Zhang Li Rong . The Enhancer Role of CYP3A4 Intron 10 in CYP3A4 Gene Expression[J]. Journal of Kunming Medical University, 2017, 38(01): 13-17.

Citation:

PDF( 196 KB)

The Enhancer Role of CYP3A4 Intron 10 in CYP3A4 Gene Expression

Funds:

基金：国家自然科学基金资助项目 (81173127); 河南省杰出青年基金资助项目 (074100510020); 河南省教育厅基础研究基金资助项目 (13A310663); 河南省科技厅基础与前沿技术研究计划基金资助项目 (142300410206); 河南省科技攻关计划基金资助项目 (162102310523);

Received Date: 2016-09-20

Abstract

Abstract

Objective To explore the regulation of CYP3A4 gene expression by CYP3A4 intron 10 and CYP3A4*1G.Methods CYP3A4 eukaryotic expression vector which promoted by CYP3A4 promoter was constructed.The forward and reverse full-length segments of CYP3A4 intron 10 (with CYP3A4*1G allele wild/mutant type) were ligated into the recombinant eukaryotic expression vector above at upstream of CYP3A4 promoter to construct CYP3A4 eukaryotic expression vector which promoted by CYP3A4 promoter and regulated by CYP3A4 intron 10 with different genotypes and directions.The vectors were transfected into Hep G2 respectively.The levels of CYP3A4 m RNA were detected by quantitative real-time PC.Results These insertion sequences and their directions were exactly correct.The expression level of CYP3A4 m RNA was higher when CYP3A4 intron 10 was inthe forward than in the reverse direction (P<0.01) ;the wild group showed higher CYP3A4 m RNA level than the mutant group (P<0.01) ;while the forward mutant group showed lower CYP3A4 m RNA level than the positive control group.Conclusion CYP3A4 intron 10 is like an enhancer functionally, which could influence the transcription of CYP3A4 promoter depending on its direction and regulation by CYP3A4*1G allele.
- Intron,
- CYP3A4*1G,
- Eukaryotic expression vector

FullText(HTML)

References(21)

References

[1]	[1]WANG D, GUO Y, WRIGHTON S A, et al.Intronic polymorphism in CYP3A4 affects hepatic expression and response to statin drugs[J].Pharmacogenomics, 2011, 11 (4) :274-286.
[2]	[2]DROGEMOLLER B, PLUMMER M, KORKIE L, et al.Characterization of the genetic variation present in CYP3A4in three South African populations[J].Frontiers in genetics, 2013, 4 (17) :1-17.
[3]	[3]GAO Y, ZHANG L R, FU Q.CYP3A4*1G polymorphism is associated with lipid-lowering efficacy of atorvastatin but not of simvastatin[J].European Journal of Clinical Pharmacology, 2008, 64 (9) :877-882.
[4]	[4]ZHANG W, CHANG Y Z, KAN Q C, et al.CYP3A4*1G genetic polymorphism influences CYP3A activity and response to fentanyl in Chinese gynecologic patients[J].European Journal Of Clinical Pharmacology, 2010, 66 (1) :61-66.
[5]	[5]HE B X, SHI L, QIU J, et al.The effect of CYP3A4*1G allele on the pharmacokinetics of atorvastatin in Chinese Han patients with coronary heart disease[J].Journal of Clinical Pharmacology, 2014, 54 (4) :462-467.
[6]	[6]YUAN J J, HOU J K, ZHANG W, et al.CYP3A4*1G Genetic Polymorphism Influences Metabolism of Fentanyl in Human Liver Microsomes in Chinese Patients[J].Pharmacology, 2015, 96 (1-2) :55-60.
[7]	[7]MIURA M, SATOH S, KAGAYA H, et al.Impact of the CYP3A4*1G polymorphism and its combination with CYP3A5 genotypes on tacrolimus pharmacokinetics in renal transplant patients[J].Pharmacogenomics, 2011, 12 (7) :977-984.
[8]石伟龙, 唐惠林, 翟所迪.CYP3A4*1G基因多态性对肾移植受者他克莫司给药剂量及血药浓度影响的系统评价[J].中国临床药理学杂志, 2015, 31 (04) :292-296.
[9]	[9]YANG W H, ZHAO D Z, HAN S N, et al.CYP3A4*1G regulates CYP3A4 intron 10 enhancer and promoter activity in an allelic-dependent manner[J].International Journal of Clinical Pharmacology and Therapeutics, 2015, 53 (8) :647-657.
[10]赵云龙, 杨卫红, 闫良, 等.CYP3A4*1G依赖的CYP3A4内含子10启动的真核表达载体的构建[J].郑州大学学报 (医学版) , 2016, 51 (2) :153-157.
[11]	[11]CHATTERJEE S, MIN L, KARUTURI R K, et al.The role of post-transcriptional RNA processing and plasmid vector sequences on transient transgene expression in zebrafish[J].Transgenic Research, 2010, 19 (2) :299-304.
[12]	[12]ROSE A B.Intron-Mediated Regulation of Gene Expression[M].Current Topics in Microbiology and Immunology, 2008, 326 (6) :277-290.
[13]	[13]PAN Y Y, CHEN R, ZHU L, et al.Utilizing modified ubi1introns to enhance exogenous gene expression in maize (Zea mays L.) and rice (Oryza sativa L.) [J].Journal of Integrative Agriculture, 2016, 15 (8) :1716-1726.
[14]	[14]DE LA TORRE C M, FINER J J.The intron and 5’distal region of the soybean Gmubi promoter contribute to very high levels of gene expression in transiently and stably transformed tissues[J].Plant Cell Reports, 2015, 34 (1) :111-120.
[15]	[15]CHOKAS A L, BICKFORD J S, BARILOVITS S J, et al.A TEAD1/p65 complex regulates the eutherian-conserved Mn SOD intronic enhancer, e RNA transcription and the innate immune response[J].Biochimica et Biophysica Acta, 2014, 1839 (11) :1205-1216.
[16]	[16]POUND L D, HANG Y, SARKAR S A, et al.The pancreatic isletβ-cell-enriched transcription factor Pdx-1 regulates Slc30a8gene transcription through an intronic enhancer[J].Biochemical Journal, 2011, 433 (1) :95-105.
[17]	[17]KRIZEK B A.Intronic sequences are required for AINTEGUMENTA-LIKE6 expression in Arabidopsis flowers[J].BMC Res Notes, 2015, 8 (556) :1-9.
[18]	[18]SRIBUDIANI Y, METZGER M, OSINGA J, et al.Variants in RET associated with Hirschsprung's disease affect binding of transcription factors and gene expression[J].Gastroenterology, 2011, 140 (2) :572-582.
[19]	[19]OGURA Y, KOU I, MIURA S, et al.A Functional SNP in BNC2 Is Associated with Adolescent Idiopathic Scoliosis[J].Am J Hum Genet, 2015, 97 (2) :337-342.
[20]	[20]CAVALLI M, PAN GANG, NORD H, et al.Looking beyond GWAS:allele-specific transcription factor binding drives the association of GALNT2 to HDL-C plasma levels[J].Lipids Health Dis, 2016, 15 (18) :1-5.
[21]	[21]VISSER M, PALSTRA R J, KAYSER M.Allele-specific transcriptional regulation of IRF4 in melanocytes is mediated by chromatin looping of the intronic rs12203592 enhancer to the IRF4 promoter[J].Hum Mol Genet, 2015, 24 (9) :2649-2661.

Relative Articles(20)

Relative Articles

[1]	Liang ZHANG, Baoquan WANG, Xifeng LEI, Xu WANG, Yang KE, Wei ZHANG. Effect of miR-29c-3p/IGF1 Molecular Axis on Activation，Proliferation and Apoptosis of Hepatic Stellate Cells. Journal of Kunming Medical University, 2023, 44(9): 7-14. doi: 10.12259/j.issn.2095-610X.S20230926
[2]	Zhongshan ZHU, Zhou YANG, Chengchuan JIANG, Xiaobing LI, Dou REN, Cheng HUANG, Weiwei ZHANG, Xiangjun LI, Shunli ZHAO. An Analysis of PLA2G1B Expression and Prognosis in Patients with Lung Adenocarcinoma. Journal of Kunming Medical University, 2022, 43(9): 70-76. doi: 10.12259/j.issn.2095-610X.S20220912
[3]	Shao-hua YANG, Zhou-Jun LIAO, Sheng HU, Mao-lin HONG, Zhi-Mei SONG, Qun WEI, Xiao-wen ZHANG. The Expression and Significance of Eukaryotic Translation Initiation Factor-5A2 in Intrahepatic Cholangiocarcinoma. Journal of Kunming Medical University, 2021, 42(5): 24-28. doi: 10.12259/j.issn.2095-610X.S20210505
[4]	Liu Chong , Cao Hui , Yang Cai Cai , Wang Zhen . . Journal of Kunming Medical University, 2020, 41(06): 32-38.
[5]	Jin Jin Hua , Li Ke Yan , Zhang Ling , Wang Yu Hui , Deng Xiao Ming . . Journal of Kunming Medical University, 2020, 41(02): 16-20.
[6]	Zhu Ke Ying , Jiang Tao , Pan Jie , Fan Zhi Xiang , Zhang Lu , Zhang Yan Jie , Wu Yan Rui , Long Li . . Journal of Kunming Medical University, 2019, 40(04): 52-56.
[7]	Duan Jun Jun , Fang Feng , Zhang Xiao Yu , Wang Jiang , Jia Xiao , He Ying Hong . Construction of WDR5 Eukaryotic Expression Vector and Its Stable Expression in LNCaP Cells. Journal of Kunming Medical University, 2017, 38(06): 1-4.
[8]	Wang Kun . Construction of ShRNA-Bmi1 Recombinant Vector and Its Effect on The Expression of hTERT in Transplantated Tumor of Nude Mice with Gallbladder Carcinoma. Journal of Kunming Medical University,
[9]	Dai Shu Ying . . Journal of Kunming Medical University,
[10]	Zhao Yu . . Journal of Kunming Medical University,
[11]	Fang Feng . . Journal of Kunming Medical University, 2015, 36(07): 1-1.
[12]	Yu Li . . Journal of Kunming Medical University,
[13]	Xu Ying . . Journal of Kunming Medical University,
[14]	Zhao Liu Fang . . Journal of Kunming Medical University,
[15]	Gu Wan Gang . . Journal of Kunming Medical University,
[16]	Chen Xi . . Journal of Kunming Medical University,
[17]	He Ying Hong . . Journal of Kunming Medical University,
[18]	Tian La Mei . . Journal of Kunming Medical University,
[19]	Bi Cheng Wei . . Journal of Kunming Medical University,
[20]	Zhan Hui . . Journal of Kunming Medical University, 2008, 29(01): 1-1.