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CTCF 绝缘子蛋白形成一种不寻常的 DNA 结构。

The CTCF insulator protein forms an unusual DNA structure.

机构信息

Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada.

出版信息

BMC Mol Biol. 2010 Dec 21;11:101. doi: 10.1186/1471-2199-11-101.

Abstract

BACKGROUND

The CTCF insulator protein is a highly conserved zinc finger protein that has been implicated in many aspects of gene regulation and nuclear organization. The protein has been hypothesized to organize the human genome by forming DNA loops.

RESULTS

In this paper, we report biochemical evidence to support the role for CTCF in forming DNA loops. We have measured DNA bending by CTCF at the chicken HS4 β-globin FII insulator element in vitro and have observed a unique DNA structure with aberrant electrophoretic mobility which we believe to be a DNA loop. CTCF is able to form this unusual DNA structure at two other binding sites: the c-myc P2 promoter and the chicken F1 lysozyme gene silencer. We also demonstrate that the length though not the sequence of the DNA downstream of the binding site is important for the ability of CTCF to form this unusual DNA structure. We hypothesize that a single CTCF protein molecule is able to act as a "looper" possibly through the use of several of its zinc fingers.

CONCLUSIONS

CTCF is able to form an unusual DNA structure through the zinc finger domain of the protein. This unusual DNA structure is formed in a directional manner by the CTCF protein. The findings described in this paper suggest mechanisms by which CTCF is able to form DNA loops, organize the mammalian genome and function as an insulator protein.

摘要

背景

CTCF 绝缘子蛋白是一种高度保守的锌指蛋白,它与基因调控和核组织的许多方面都有关联。该蛋白被假设通过形成 DNA 环来组织人类基因组。

结果

在本文中,我们报告了生化证据,支持 CTCF 在形成 DNA 环中的作用。我们已经测量了 CTCF 在鸡 HS4β-球蛋白 FII 绝缘子元件中的体外 DNA 弯曲,并观察到一种具有异常电泳迁移率的独特 DNA 结构,我们认为这是一种 DNA 环。CTCF 能够在另外两个结合位点形成这种异常的 DNA 结构:c-myc P2 启动子和鸡 F1 溶菌酶基因沉默子。我们还证明,尽管结合位点下游的 DNA 序列不重要,但 DNA 的长度对于 CTCF 形成这种异常的 DNA 结构的能力很重要。我们假设单个 CTCF 蛋白分子能够充当“环制造者”,可能通过使用其几个锌指。

结论

CTCF 能够通过蛋白的锌指结构形成一种异常的 DNA 结构。这种异常的 DNA 结构是由 CTCF 蛋白以定向的方式形成的。本文所述的发现表明了 CTCF 能够形成 DNA 环、组织哺乳动物基因组并作为绝缘子蛋白发挥功能的机制。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/acf4/3014928/e469c530c609/1471-2199-11-101-1.jpg

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