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，染色质的高阶组织在基因中很重要 表情。然而，关于基因组是如何在细胞内折叠和组织的，人们知之甚少 特定的基因以细胞类型特定的方式受到适当的调控。我们的研究小组 发现了一种核蛋白SATB1，它具有独特的‘基因组组织者’功能。我们 发现SATB1在异染色质周围有一种像笼子一样的蛋白质分布，这 蛋白质通过连接特定的DNA序列来折叠染色质。SATB1作为着陆器 用于组装染色质重塑/修饰复合体的平台 DNA序列，从而调节大量基因的表达。因此，SATB1设置为 一个功能强大的核体系结构，称为“SATB1网络”，因为它建立了一个 具有重新编程基因表达能力的调控网络。事实上，我们最新的 数据表明，SATB1核结构在细胞获得新功能方面起着重要作用。我们 计划研究SATB1在不同类型癌症的进展中的作用 利用条件性SATB1基因敲除小鼠发育一些成体祖细胞。我们会 还要研究SATB1如何在空间上组织细胞核中的基因组位置，以及它是否对 在细胞记忆的基础机制中。