Non B DNA Structure with Chemical Carcinogens

含有化学致癌物质的非 B DNA 结构

• 批准号: 7909158
• 负责人: Terumi Kohwi-Shigematsu
• 金额: $ 32.6万
• 依托单位: UNIVERSITY OF CALIF-LAWRENC BERKELEY LAB
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-08-01 至 2011-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7909158
• 关键词: Adult; Architecture; Cell Nucleus; Cells; Chromatin; Complex; DNA Sequence; DNA Structure; Data; Development; Gene Expression; Genes; Genome; Genomics; Heterochromatin; Knockout Mice; Memory; Nuclear; Nuclear Protein; Nuclear Proteins; Research; Role; Stem cells; cancer type; cell type; chemical carcinogen; chromatin remodeling; programs; protein distribution; protein folding

Accumulated evidence suggests that higher-order organization of chromatin is important in gene expression. However, little is known about how genomes are folded and organized in the cell so that specific genes are properly regulated in a cell-type specific manner. Our research group identified a nuclear protein SATB1, which has a unique function as a 'genome organizer'. We found that SATB1 has a 'cage-like' protein distribution surrounding the heterochromatin, and this protein folds chromatin by tethering specialized DNA sequences. SATB1 serves as a landing platform for the assembly of chromatin remodeling/modifying complexes with the specialized DNA sequences, thereby regulating expression of a large body of genes. Thus, SATB1 sets up a functional nuclear architecture, referred to as 'the SATB1 network', since it establishes a regulatory network with the capacity to re-program gene expression. In fact, our most recent data show that the SATB1 nuclear architecture is important in cells acquiring new functions. We plan to investigate the roles of SATB1 in the progression of different types of cancer and in development of some adult progenitor cells using conditional SATB1 knockout mice. We will also study how SATB1 spatially organizes genomic loci in the nuclei and whether it contributes in the mechanisms underlying cell memory.

越来越多的证据表明，染色质的高级结构在基因表达中起着重要的作用。 表情然而，人们对基因组在细胞中是如何折叠和组织的知之甚少， 特定的基因以细胞类型特异性的方式被适当地调节。本课题组 鉴定了核蛋白SATB 1，其具有作为“基因组组织者”的独特功能。我们 发现SATB 1在异染色质周围有一个“笼状”蛋白分布， 蛋白质通过固定特殊的DNA序列折叠染色质。SATB 1用作着陆点 用于组装染色质重塑/修饰复合物的平台， DNA序列，从而调节大量基因的表达。因此，SATB 1设置 一个功能性的核架构，被称为“SATB 1网络”，因为它建立了一个 具有重新编程基因表达能力的调节网络。事实上，我们最近的 数据显示SATB 1核结构在细胞获得新功能中是重要的。我们 计划研究SATB 1在不同类型癌症进展中的作用， 使用条件性SATB 1敲除小鼠开发一些成体祖细胞。我们将 我还研究了SATB 1如何在细胞核中空间组织基因组位点，以及它是否有助于 细胞记忆的机制。