Investigation of X chromosome organization before the onset of X-inactivation

X 失活发生前 X 染色体组织的研究

• 批准号: 8387975
• 负责人: BARBARA PANNING
• 金额: $ 29.58万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-07-20 至 2016-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8387975
• 关键词: Binding Sites; Biological Assay; Cell Nucleus; Cells; Chromatin; Chromosome Structures; DNA Sequence; Data; Development; Diploidy; Disease; Dosage Compensation (Genetics); Elements; Ensure; Female; Fluorescent in Situ Hybridization; Gene Dosage; Gene Expression; Gene Expression Regulation; Genes; Genome; Health; Human; Investigation; Link; Location; Malignant Neoplasms; Mediating; Molecular; Nuclear; Play; Positioning Attribute; Process; Progeria; Proteins; Regulatory Element; Rest; Rett Syndrome; Role; System; Testing; Trans-Activators; X Chromosome; X Inactivation; base; chromatin immunoprecipitation; chromosome X; autosome translocation syndrome; genetic analysis; human disease; insight; male

DESCRIPTION (provided by applicant): The position of substructures and DNA sequences within the nucleus is highly organized, and this organization plays a role in regulating chromatin-dependent processes, such as gene expression. X chromosome inactivation is an experimentally amenable example of a phenomenon in which regulated changes in the location of specific DNA sequences is implicated in control of gene expression. In mammalian female cells, one X chromosome is silenced for dosage compensation of X-linked genes between males and females, and this process is essential for female survival. Here, we propose to investigate the molecular basis of the regulated changes in X chromosome nuclear organization that accompany X-inactivation. The insights gained are likely to be more generally applicable, since many of the factors that regulate X-inactivation also regulate gene expression in other contexts. PUBLIC HEALTH RELEVANCE: Early in mammalian development, one of the X chromosomes is silenced in each cell, to equalize X- linked gene dosage between XY males and XX females. X-inactivation is essential for survival of mammalian females, and many of the factors that regulate X-inactivation also regulate gene expression in other contexts. We propose to study the molecular basis of changes in X chromosome organization during X- inactivation. This will provide important information about the role of nuclear organization in X- inactivation and will be relevant to understanding how nuclear organization impacts gene expression for the rest of the genome.

描述（由申请人提供）：细胞核中的亚结构和DNA序列的位置是高度组织的，该组织在调节染色质依赖性过程中起作用，例如基因表达。 X染色体灭活是一个实验上可正常的例子，其中一种现象的例子，其中调节特定DNA序列位置的变化与控制基因表达有关。在哺乳动物雌性细胞中，一个X染色体对男性和女性之间的X连锁基因的剂量补偿保持沉默，这对于女性生存至关重要。在这里，我们建议研究伴随X灭活的X染色体核组织调节变化的分子基础。获得的见解可能更普遍适用，因为许多调节X灭活的因素也在其他情况下调节基因表达。 公共卫生相关性：在哺乳动物发育初期，每个细胞中的X染色体之一是沉默的，以均衡XY雄性和XX女性之间的X链接基因剂量。 X灭活对于哺乳动物女性的生存至关重要，许多调节X灭活的因素也调节其他情况下的基因表达。我们建议研究X灭活过程中X染色体组织变化的分子基础。这将提供有关核组织在X灭活中的作用的重要信息，将是 与了解核组织如何影响基因组的其余部分有关。