Insulator function and CTCF

绝缘体功能和CTCF

• 批准号: 7593565
• 负责人: Gary Felsenfeld
• 金额: $ 36.46万
• 依托单位: NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/7593565
• 关键词: Affinity; Attention; Binding; CCCTC-binding factor; Cell Nucleus; Chickens; Chromatin; DNA; DNA Sequence; Elements; Enhancers; Gene Expression; Localized; Nucleolar Proteins; Proteins; Range; Regulation; Role; Site; Surveys; Tertiary Protein Structure; beta Globin; design; imprint; nucleophosmin; prevent

We have focused attention on the 1.2 kb insulator DNA sequence at the 5 end of the chicken beta-globin locus, and elements upstream of it. This insulator is capable both of blocking the influence of outside enhancers and of preventing the encroachment of condensed chromatin that might shut down expression of the entire region. We have shown previously that enhancer blocking activity is associated with binding of a single protein, CTCF, to a site within the enhancer. We have shown that this protein is responsible for regulation of imprinted gene expression at several imprinted loci. In order to understand the mechanism of action of CTCF we have determined the minimum CTCF fragment that can bind to its target DNA site with full affinity. We have also extended our earlier studies showing that CTCF molecules interact with one another. This provides important information for design of proteins that can modulate CTCF function within the nucleus. In earlier studies we also showed that CTCF interacts with the nucleolar protein nucleophosmin. We are now extending this to determine what other proteins interact with CTCF and could modulate its function, particularly in stabilizing long range interactions in the nucleu

我们将注意力集中在鸡β-珠蛋白基因座的5端的1.2 kb绝缘子DNA序列以及其上游的元素上。该绝缘子能够阻止外部增强剂的影响，也可以防止凝结染色质的侵蚀，这可能会阻止整个区域的表达。我们先前已经证明，增强子阻断活性与单个蛋白CTCF与增强子内部位置的结合有关。我们已经表明，该蛋白质负责调节几个印迹基因座的印迹基因表达。为了了解CTCF的作用机理，我们已经确定了最小CTCF片段，该片段可以与其目标DNA位点具有完全亲和力结合。我们还扩展了早期的研究，表明CTCF分子相互相互作用。 这为可以调节核中CTCF功能的蛋白质设计提供了重要信息。 在较早的研究中，我们还表明CTCF与核仁蛋白核磷脂相互作用。现在，我们正在扩展它以确定其他蛋白质与CTCF相互作用并可以调节其功能，尤其是在稳定核中的远距离相互作用时