IDENTIFICATION OF REGULATORY MOTIFS IN ABC GENES BY COMPARATIVE GENOMIC ANALYSIS

通过比较基因组分析鉴定 ABC 基因的调控基序

• 批准号: 7960063
• 负责人: CAROLYN J MATTINGLY
• 金额: $ 22.63万
• 依托单位: MOUNT DESERT ISLAND BIOLOGICAL LAB
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-05-23 至 2010-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7960063
• 关键词: ABCC1 gene; Arsenic; Carcinogens; Chemicals; Collaborations; Comparative Genomic Analysis; Computer Retrieval of Information on Scientific Projects Database; Congenital Abnormality; Defect; Development; Disease; Dose; Embryo; Environment; Environmental Pollution; Environmental Risk Factor; Etiology; Exposure to; Faculty; Functional RNA; Funding; Gene Targeting; Genes; Genetic; Genomics; Goals; Grant; Human; Incidence; Institution; Maine; Malignant Neoplasms; Mediating; Pathway interactions; Perinatal Exposure; Pharmacology and Toxicology; Physiological Processes; Play; Protein Family; Research; Research Personnel; Resources; Risk Factors; Role; Source; Spontaneous abortion; Teratogens; Tetrachlorodibenzodioxin; Toxic effect; United States National Institutes of Health; Work; Zebrafish; comparative; craniofacial; functional genomics; human disease; member; novel; stem

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Project #1: The ABC superfamily is one of the largest known families of proteins. Members of the ABCB and ABCC subfamilies play significant roles in toxicology, pharmacology, and disease; however, mechanisms that regulate their expression are not well understood. The goal of this project is to identify functionally significant regulatory motifs in non-coding regions of ABCB and ABCC genes using comparative genomic and motif-finding strategies. This work is being done in collaboration with Drs. Tony Planchart (MDIBL, INBRE faculty) and Clare Congdon (USM; INBRE faculty). I further explored the following projects that stemmed from project #1, also in collaboration with Dr. Planchart. Project #2: Perturbation of defense pathways by low-dose arsenic exposure in zebrafish embryos Exposure to chemicals is a risk factor in the interplay between genetics, the environment and human disease. Adverse developmental consequences of exposure to arsenic in humans are largely unknown despite the potential for in utero exposure worldwide and results from studies suggesting that there is cause for concern (e.g., increased incidence of cancers, spontaneous abortions). This study aims to identify genes targeted by low levels of arsenic during vertebrate development to better understand mechanisms underlying arsenic toxicity. Project #3: Identification of a novel target of 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) involved in craniofacial development The etiology of many birth defects involves interactions between environmental factors and genes that modulate important physiological processes. The environmental contaminant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is found ubiquitously in the environment and is a known carcinogen and teratogen; however, the mechanisms underlying its toxicity are unclear. This study aimed to identify targets of TCDD potentially responsible for mediating exposure-related craniofacial defects.

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 项目一： ABC超家族是已知最大的蛋白质家族之一。 ABCB和ABCC亚家族的成员在毒理学、药理学和疾病中发挥重要作用;然而，调节其表达的机制还不清楚。本项目的目标是利用比较基因组学和基序发现策略，在ABCB和ABCC基因的非编码区中鉴定功能上重要的调控基序。 这项工作正在与Tony Planchart博士（MDIBL，INBRE教师）和克莱尔Congdon（USM; INBRE教师）合作完成。 我进一步探索了以下项目，这些项目源于项目#1，也是与Planchart博士合作。 项目#2：低剂量砷暴露对斑马鱼胚胎防御途径的干扰 接触化学品是遗传、环境和人类疾病之间相互作用的一个风险因素。人类接触砷的不良发育后果在很大程度上是未知的，尽管全世界子宫内接触的可能性和研究结果表明，有理由关注（例如，癌症发病率增加，自然流产）。本研究旨在鉴定脊椎动物发育过程中低水平砷的靶基因，以更好地了解砷毒性的机制。 项目#3：确定参与颅面发育的2，3，7，8-四氯二苯并对二恶英（TCDD）的新靶点 许多出生缺陷的病因学涉及环境因素和调节重要生理过程的基因之间的相互作用。环境污染物2，3，7，8-四氯二苯并-对-二恶英（TCDD）在环境中普遍存在，是已知的致癌物和致畸物;然而，其毒性机制尚不清楚。本研究的目的是确定目标的TCDD可能负责调解手术相关的颅面缺损。