Control of centromeric chromatin structure in Drosophila

果蝇着丝粒染色质结构的控制

• 批准号: 6932359
• 负责人: TAKEHITO FURUYAMA
• 金额: $ 5.15万
• 依托单位: FRED HUTCHINSON CANCER RESEARCH CENTER
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-09-01 至 2007-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6932359
• 关键词: DNA methylation; DNA replication; Drosophilidae; SDS polyacrylamide gel electrophoresis; autoradiography; centromere; chromatin; chromosome movement; eukaryote; heterochromatin; immunoprecipitation; nucleic acid structure; postdoctoral investigator; western blottings

DESCRIPTION (provided by applicant): The centromere, a highly specialized region found on each chromosome, plays a critical role in the segregation of chromosomes. Failure to maintain proper centromeric function results in aneuploidy, leading to various diseases, such as cancer. However, the centromeres represent the least characterized region of eukaryotic genomes. All eukaryotic centromeres studied to date are packaged into a specialized chromatin domain that contains centromeric histone H3 (cenH3). The long-term goal of this proposal is to understand how proper centromeric structure is formed. Centromeric chromatin is arranged in interspersed blocks of cenH3 and canonical H3 nucleosomes in flies and humans, which is hypothesized to aid in three-dimensional folding of the centromeric region; however, the regulation of DNA replication and assembly of centromeric chromatin are poorly understood. In this proposal, 1) physical relationships between cenH3 and DNA replication / chromatin assembly factors will be investigated in Drosophila; and 2) cenH3 associated sequence will be isolated. Characterization of both protein factors and DNA elements that act in concert at the centromeres will lead to better understanding of centromere formation.

描述（由申请人提供）：着丝粒是每条染色体上发现的高度专业化的区域，在染色体分离中起着关键作用。未能维持适当的着丝粒功能会导致非整倍体，从而导致各种疾病，例如癌症。然而，着丝粒代表真核基因组中特征最少的区域。迄今为止研究的所有真核着丝粒都被包装到包含着丝粒组蛋白 H3 (cenH3) 的特殊染色质结构域中。该提案的长期目标是了解正确的着丝粒结构是如何形成的。在果蝇和人类中，着丝粒染色质排列在 cenH3 和规范 H3 核小体的散布块中，推测这有助于着丝粒区域的三维折叠；然而，人们对 DNA 复制和着丝粒染色质组装的调控知之甚少。在该提案中，1）将在果蝇中研究cenH3和DNA复制/染色质组装因子之间的物理关系； 2) cenH3相关序列将被分离。对着丝粒协同作用的蛋白质因子和 DNA 元件进行表征将有助于更好地了解着丝粒的形成。