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）：细胞核内的子结构和 DNA 序列的位置是高度组织化的，并且这种组织在调节染色质依赖性过程（例如基因表达）中发挥着作用。 X 染色体失活是一种经过实验证实的现象，其中特定 DNA 序列位置的调节变化与基因表达的控制有关。在哺乳动物雌性细胞中，一条 X 染色体被沉默，以补偿雄性和雌性之间 X 连锁基因的剂量补偿，这一过程对于雌性的生存至关重要。在这里，我们建议研究伴随 X 失活而发生的 X 染色体核组织调节变化的分子基础。所获得的见解可能更普遍适用，因为许多调节 X 失活的因素也在其他情况下调节基因表达。 公共卫生相关性：在哺乳动物发育早期，每个细胞中的一条 X 染色体被沉默，以平衡 XY 雄性和 XX 雌性之间的 X 连锁基因剂量。 X 失活对于雌性哺乳动物的生存至关重要，许多调节 X 失活的因素也在其他情况下调节基因表达。我们建议研究 X 失活过程中 X 染色体组织变化的分子基础。这将提供有关核组织在 X 失活中的作用的重要信息，并将 与理解核组织如何影响基因组其余部分的基因表达相关。