REGULATION OF X-CHROMOSOME EXPRESSION IN MAMMALS

哺乳动物 X 染色体表达的调控

• 批准号: 3333343
• 负责人: VERNE M CHAPMAN
• 金额: $ 22万
• 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/3333343
• 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.

在胚胎发生的早期，X染色体失活的开始