LINKER HISTONE/DNA INTERACTIONS

连接子组蛋白/DNA 相互作用

• 批准号: 2187985
• 负责人: KENSAL E. VAN HOLDE
• 金额: $ 18.59万
• 依托单位: OREGON STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1994
• 资助国家: 美国
• 起止时间: 1994-08-01 至 1998-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2187985
• 关键词: DNA binding protein; chemical binding; chemical stability; chromatin; crosslink; genetic regulation; histones; molecular site; nonhistone nucleoprotein; nucleic acid sequence; nucleic acid structure; nucleosomes; polymerase chain reaction

Recent evidence from our laboratory indicates that the so-called "linker" histones (H1, H5, and their variants) can bind to certain DNA structures and sequences much more specifically than hitherto believed. In particular, these histones strongly bind to DNA crossover structures, typified by the four-way junction. These are the same structures favored by an abundant class of high mobility group proteins (HMG 1/2), and resemble the DNA structure at the entrance and exit from the nucleosome. Linker histones and HMG1 binding appear to be related to general mechanisms of genetic repression and expression. We propose a detailed investigation of this selective binding, including quantitation of binding by intact histones and their globular domains to the junction, and competition between histone variants and HMGI for such binding. The binding/competition experiments will then be extended to studies utilizing nucleosomes, as a more direct model of the in vivo structure. A second area of study will utilize PCR amplification methods in an attempt to discover DNA sequences or sequence types exhibiting strong linker histone binding. These will then be used in studies of the effects of such binding on DNA conformation.

我们实验室的最新证据表明，所谓的“连接体” 组蛋白（H1、H5及其变体）可以与某些DNA结构结合 和序列比迄今为止所认为的更具体。 在 特别地，这些组蛋白强烈地结合到DNA交换结构， 典型的是四路交叉口。 这些都是同样的结构 由丰富的一类高迁移率族蛋白（HMG 1/2），和 类似于核小体入口和出口处的DNA结构。 连接体组蛋白和HMG 1结合似乎与一般的 遗传抑制和表达的机制。我们提出了一个详细的 这种选择性结合的研究，包括结合的定量 通过完整的组蛋白及其球状结构域连接， 组蛋白变体和HMGI之间竞争这种结合。 的 然后，结合/竞争实验将扩展到利用 核小体，作为体内结构的更直接的模型。 第二个研究领域将利用PCR扩增方法， 试图发现DNA序列或序列类型表现出强的 接头组蛋白结合。 这些将用于研究 DNA构象上的这种结合。