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[鸡β-珠蛋白基因:用于在基因组结构域水平研究转录调控的模型系统]

[The chicken beta-globin genes: a model system for studying transcription regulation at the level of genomic domains].

作者信息

Ul'ianov S V, Gavrilov A A

出版信息

Mol Biol (Mosk). 2012 Sep-Oct;46(5):683-98.

Abstract

In the last quarter of the XX century, as a result of studies performed on a number of model systems, a hypothesis was formulated according to which the genome of higher eukaryotes consists of functionally isolated areas named genomic domains. Each domain includes one or more genes and a regulatory system that is normally active only in respect of this domain and allows it to achieve the regulatory autonomy of the neighboring chromosome regions. A genomic domain is characterized by the spectra of covalent histone modifications which define the boundaries of the domain and the degree of chromatin condensation within it, and so, the probability of transcription activation of genes within the domain. Development of the domain hypothesis of genome organization became possible to a large extent through the study of mechanisms of transcriptional regulation of the globin genes in vertebrates. One of the most popular models in this field of molecular biology is the chicken beta-globin gene domain. Based on this model system, the fundamental principles of complex enhancer action in higher eukaryotes have been described, the properties of insulators and functional units of enhancers and promoters have been studied, the influence of covalent histone modifications on the level of chromatin condensation and their role in the regulation of transcription within the domain have been investigated. In this review we summarize the data on the study of the chicken beta-globin gene domain, as well as consider the domain hypothesis of eukaryotic genome organization.

摘要

在20世纪的最后25年里,通过对一些模型系统进行的研究,形成了一种假说,即高等真核生物的基因组由功能上相互隔离的区域组成,这些区域被称为基因组结构域。每个结构域包含一个或多个基因以及一个调控系统,该调控系统通常仅针对此结构域具有活性,并使其能够实现与相邻染色体区域的调控自主性。基因组结构域的特征在于共价组蛋白修饰的谱,这些修饰定义了结构域的边界以及其中染色质浓缩的程度,进而决定了结构域内基因转录激活的概率。基因组组织的结构域假说的发展在很大程度上得益于对脊椎动物珠蛋白基因转录调控机制的研究。该分子生物学领域最流行的模型之一是鸡β-珠蛋白基因结构域。基于这个模型系统,已经描述了高等真核生物中复杂增强子作用的基本原理,研究了绝缘子以及增强子和启动子功能单元的特性,还研究了共价组蛋白修饰对染色质浓缩水平的影响及其在结构域内转录调控中的作用。在这篇综述中,我们总结了关于鸡β-珠蛋白基因结构域研究的数据,并探讨了真核生物基因组组织的结构域假说。

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