REGULATION OF X-CHROMOSOME EXPRESSION IN MAMMALS

哺乳动物 X 染色体表达的调控

• 批准号: 3333345
• 负责人: VERNE M CHAPMAN
• 金额: $ 19.69万
• 依托单位: ROSWELL PARK CANCER INSTITUTE
• 依托单位国家: 美国
• 财政年份: 1990
• 资助国家: 美国
• 起止时间: 1990-09-01 至 1993-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3333345
• 关键词: DNA methylation; alleles; alpha galactosidase; autosome; centrifugation; chromosome translocation; developmental genetics; early embryonic stage; electrophoresis; embryo /fetus; gene expression; gene induction /repression; genetic manipulation; genetic markers; hybrid cells; hypoxanthine phosphoribosyltransferase; laboratory mouse; linkage mapping; mammalian embryology; mutant; nucleic acid probes; oogenesis; phosphoglycerate kinase; sex chromosomes; sperm; tissue mosaicism

The initiation of X inactivation during early embryogenesis and the subsequent maintenance of the inactive X condition throughout development are central issues in the X-inactivation process. These features and the succeeding reactivation during oogenesis are unique developmental changes which produce the coordinate regulation of an entire X chromosome. This proposal is a broadly based approach to studying the X-inactivation process in the mouse. Our experimental strategies draw upon using X-chromosome gene variation we have recovered from a wide sampling of the mouse gene pool to follow the expression of specific X chromosomes. We have extended this strategy to identifying DNA variation which can be used to follow DNA methylation on active and inactive X-chromosome genes. We are now in a position to extend our use of naturally occurring variation of X chromosome genes to efficiently screen mutagen treated stocks for additional X chromosome markers and to identify mutations which provide an opportunity to pursue a genetic analysis of X-chromosome regulation during the inactivation process. We are also extending the use of biochemical markers of X-chromosome genes to examine the expression of X-chromosome genes in X;autosome translocations. The expression of genes which are either proximal or distal to the translocation will provide some insight into the site(s) which establish X-chromosome identity in the inactivation process. This proposal also describes experiments to study X-chromosome reactivation in embryonal carcinoma cell-somatic cell hybrids. This work will provide important information about the inactivation and reactivation process and it offers an opportunity to develop new experimental approaches to studying X-chromosome regulation.

胚胎发生早期X染色体失活的起始和 随后在整个发育过程中保持不活跃的X状态 是X染色体失活过程中的核心问题 这些特点和 卵子发生过程中的后续再激活是独特的发育变化 产生整个X染色体的协调调节。 这一建议是一个基础广泛的方法来研究X-失活 鼠标中的过程。 我们的实验策略利用了 X染色体基因变异，我们已经恢复了广泛的抽样， 小鼠基因库，以跟踪特定X染色体的表达。 我们 我已经将这一策略扩展到识别DNA变异， 跟踪活跃和不活跃X染色体基因的DNA甲基化。 我们 现在能够扩展我们对自然发生的变异的使用， X染色体基因，以有效筛选诱变剂处理的原种， 另外的X染色体标记物，并鉴定突变， 有机会进行X染色体调控的遗传分析， 失活过程。 我们也在扩大X染色体基因生化标记的使用范围 检测X染色体基因在X染色体常染色体中的表达 易位 基因的表达，无论是近端或 易位远端将提供对位点的一些了解 其在失活过程中建立X染色体的同一性。 这 该提案还描述了研究X染色体再激活的实验， 胚胎癌细胞-体细胞杂种。 这项工作将提供 关于灭活和再活化过程的重要信息， 它提供了一个发展新的实验方法来研究 X染色体调控