SYSTEMATIC DELETION ANALYSIS OF THE XIST GENE

Xist 基因的系统缺失分析

• 批准号: 6402664
• 负责人: REBECCA M BOUMIL
• 金额: $ 4.2万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-07-01 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6402664
• 关键词: artificial chromosomes; cell differentiation; chromosome deletion; embryonic stem cell; gene expression; gene induction /repression; heterochromatin; laboratory mouse; sex chromosomes; tissue /cell culture; transfection

Female mammals carry two copies of the X chromosome as compared to males with an XY complement. This double dosage of X genes must be compensated for and is so by the transcriptional inactivation of one X chromosome. Mistakes in the inactivation process can be observed in human females as skewed inactivation pattern resulting in genetic abnormalties. The long term objective of this research is to broaden the understanding of the process and regulation of mammalian X chromosome inactivation. A key player in the X-inactivation process is the Xist gene. An established genetic assay will be used to study the Xist gene and analyze deletion mutations in order to elucidate the essential domains of the gene and the step in which the product is involved. Systematic overlapping deletions spanning the Xist gene will be created in a yeast vector system. These deletion mutation constructs will be analyzed by a transgenic functional assay for deletions that abolish the inactivation process. Identifying of critical domains within this gene will help to elucidate how the gene functions as well as provide insight to the inactivation process.

与携带 XY 互补染色体的雄性哺乳动物相比，雌性哺乳动物携带两个 X 染色体拷贝。 这种双倍剂量的 X 基因必须通过一条 X 染色体的转录失活来补偿。 在人类女性中可以观察到失活过程中的错误，因为失活模式的倾斜会导致遗传异常。 这项研究的长期目标是扩大对哺乳动物 X 染色体失活过程和调控的理解。 X 失活过程中的一个关键角色是 Xist 基因。 已建立的基因检测将用于研究 Xist 基因并分析缺失突变，以阐明该基因的基本结构域以及该产物所涉及的步骤。 将在酵母载体系统中创建跨越 Xist 基因的系统重叠删除。 这些缺失突变构建体将通过转基因功能测定来分析消除失活过程的缺失。识别该基因内的关键域将有助于阐明该基因如何发挥作用，并深入了解失活过程。