Methylation analysis of the gene ADRB2

ADRB2基因甲基化分析

• 批准号: 7588589
• 负责人: GREGORY A HAWKINS
• 金额: $ 7.4万
• 依托单位: WAKE FOREST UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-06-19 至 2011-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7588589
• 关键词: ADRB2 gene; Agonist; Asthma; Binding; Candidate Disease Gene; Cell Proliferation; Cells; Chronic Obstructive Airway Disease; Code; DNA; DNA Methylation; Data; Epigenetic Process; Future; Gene Expression; Gene Expression Regulation; Gene Proteins; Genes; Genetic; Genetic Polymorphism; Genotype; Health; Human; Incubated; Investigation; Measures; Messenger RNA; Methylation; Monitor; Obstructive Lung Diseases; Pattern; Pharmacogenetics; Pilot Projects; Proliferating; Proteins; Reverse Transcriptase Polymerase Chain Reaction; Role; Site; Smooth Muscle Myocytes; Tachyphylaxis; Testing; Time; base; cell type; exposed human population; field study; promoter; protein expression; radioligand; receptor; receptor expression; research study; respiratory smooth muscle; response

Epigenetic regulation of gene expression is an emerging concept relevant to human health. This proposal's objective is to investigate the epigenetic control of ADRI32 expression in cells relevant to obstructive lung .=. �'m exposed to a a-agonist, the degree of DNA methylation is increased in the promoter and coding region of the gene for the 13-agonist receptor, ADRB2. Based on the classical function that DNA methylation blocks or decreases gene expression, we hypothesize that long term exposure of HASM cells to 13-agonist increases methylation of ADRB2 and resulting in decreased expression of ADRB2. This decrease in ADR132 could be a major mechanism contributing to tachyphylaxis to 13-agonist treatment in asthma and COPD. In this proposed pilot study, we will test our hypothesis by: 1) Performing methylation specific sequencing on ADRI32 to localize and quantitate methylated CpG sites in DNA isolated from HASM cells exposed to 13-agonists; 2) Assessing the effects of ADR2 methylation on gene expression. v+3 �:3 W-0 =:r a:' �--, any 0-0 disease. We have recent preliminary data showing that in human airway smooth muscle (HASM) cells U).2 M-0 .4) `Z-_ Gam. pro. -0a� >,Q tom/! a--

基因表达的表观遗传调控是一个与人类健康相关的新兴概念。本提案的目的是研究与阻塞性肺相关的细胞中 ADRI32 表达的表观遗传控制。 .=. �我 暴露于α-激动剂后，13-激动剂受体ADRB2基因的启动子和编码区的DNA甲基化程度增加，基于DNA甲基化阻断或降低基因表达的经典功能，我们竞争了那么长时间。 HASM 细胞长期暴露于 13 激动剂会增加 ADRB2 的甲基化并导致 ADRB2 表达减少，这种 ADR132 的减少可能是导致快速耐受的主要机制。 13 激动剂治疗哮喘和慢性阻塞性肺病 在这项拟议的试点研究中，我们将通过以下方式检验我们的假设： 1) 对 ADRI32 进行甲基化特异性测序，以定位和定量从暴露于 13 激动剂的 HASM 细胞中分离的 DNA 中的甲基化 CpG 位点； ) 评估 ADR2 甲基化对基因表达的影响。 v+3 :3 W-0 =:r 一个：' �--, 任何 0-0 我们最近的初步数据表明，在人类气道平滑肌（HASM）细胞中存在这种疾病。 U).2 M-0 .4) `Z-_ 甘。 亲。 -0a� >,问 汤姆/！ 一个 -