SYSTEMATIC DELETION ANALYSIS OF THE XIST GENE

Xist 基因的系统缺失分析

• 批准号: 2862114
• 负责人: REBECCA M BOUMIL
• 金额: $ 3.03万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-02-01 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/2862114
• 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.

与具有XY补体的男性相比，女性哺乳动物携带两份X染色体副本。 X基因的这种双重剂量必须得到补偿，并且可以通过一个X染色体的转录失活。 在失活过程中的错误可以在人类女性中观察到偏斜的失活模式，从而导致遗传异常。 这项研究的长期目标是扩大对哺乳动物X染色体灭活过程和调节的理解。 X灭活过程中的关键参与者是XIST基因。 已建立的遗传测定法将用于研究XIST基因并分析缺失突变，以阐明基因的基本域和涉及产品的步骤。 跨越XIST基因的系统重叠删除将在酵母向量系统中创建。 这些缺失突变构建体将通过转基因功能分析来分析废除失活过程的缺失。识别该基因中的关键域将有助于阐明基因的功能以及对失活过程的见解。