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2015年11月11日讯/生物谷BIOON/日内瓦大学 (UNIGE)和瑞士洛桑联邦理工大学(EPFL) 的研究人员正在研究控制核小体动态性及其如何影响基因的表达。他们发现所有启动子依据不同的核小体稳定状态可以分为两个不同的类型。一种类型是以动态的存在为特点的不稳定的核小体，属于高度表达基因，参与控制细胞生长和分裂过程。另一种类型含有稳定的核小体，属于不经常表达的基因。该发现发表在《分子细胞》上。
约两米的线性DNA如何包含在哺乳动物细胞中并适应大约0.01毫米直径的核仁？这是在核小体的帮助下完成的。当一个给定的基因需要转录来组成新的蛋白质时，其启动子区域必须打开核小体，这样就可以参与启动转录过程。
与生长有关的高表达基因
“重要的是要理解核小体是如何运动或重组的，因为这将影响DNA启动子，进而影响相应基因的表达” David Shore教授解释道。核小体形成的动力帮助理解为什么有些基因高表达，比如那些参与正常或恶性增长的基因，而其他的如应激基因在正常情况下很少表达。
研究人员对存在于每一个酵母基因启动子的核小体进行了研究。这种单细胞真菌被用来作为一种模式生物，因为它的功能在许多方面像哺乳动物细胞。就像人体细胞、酵母也拥有所谓的“脆弱”核小体。它们不抵抗某些特定的酶，其性质和功能仍然难以捉摸。
一个独特类型的动态核小体
“我们已经揭示了两种类型的启动子及不同的脆弱的核小体的存在。” Slawomir Kubik说。科学家们还发现启动子的类型包含“脆弱”核小体与高水平的转录密切相关。他们推测，“脆弱”核小体的动态特性对蛋白启动子的转录有非常重要的作用。“基因组大部分时间处于一种非常紧凑的状态，核小体缠绕DNA 类似弹簧一样。我们相信动态核小体高表达基因的存在有助于迅速解除这种“弹簧”” David Shore说。（基因宝jiyinbao.com）
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生物谷推荐阅读： Researchers from the University of Geneva (UNIGE) and the Ecole polytechnique fédérale de Lausanne (EPFL), Switzerland, are studying the mechanisms controlling nucleosome dynamics and how this affects gene expression. They discovered all promoters could be classified into two distinct types differing by their state of nucleosome stability. One type, characterized by the presence of dynamic, unstable, nucleosomes, is found at highly expressed genes, such as those involved in the control of cell growth and division. The other type, which contains well-known stable nucleosomes, is located at less frequently expressed genes. The interplay of different molecular actors involved in nucleosome destabilization is described in the journal Molecular Cell.
How can about two meters of linear DNA contained in a mammalian cell fit into a nucleus of roughly 0.01 mm diameter? This is done with the help of nucleosomes, basic units made of proteins around which a segment of DNA is wound. When a given gene needs to be transcribed to create new proteins, its promoter region must be unwrapped from the nucleosome so that it can be accessed by the factors involved in initiating the transcription process.
Growth-related genes are highly expressed
“It is important to understand how nucleosomes are moved, ejected or restructured, as this will affect the accessibility of promoter DNA, which in turn influences the expression of the corresponding genes”, explains David Shore, professor at the Department of Molecular Biology of the Faculty of Science at UNIGE. The dynamics of nucleosome formation and positioning in promoters may, for example, help to understand why some genes are highly expressed, such as those involved in normal or malignant growth, while others, such as stress-induced genes, are only rarely expressed under normal conditions.
In collaboration with researchers at the Department of Computer Science (UNIGE) and the Swiss Institute of Bioinformatics at EPFL, David Shore’s team has undertaken to characterize nucleosomes present in every gene promoter of yeast DNA. This unicellular fungus is used as a model organism because it functions in many respects like a mammalian cell. As do human cells, yeast also possesses so-called ‘fragile’ nucleosomes. Discovered by chance and termed ‘fragile’ because they don’t resist as well as the others to certain enzymes, their nature and function remained elusive.
A unique type of dynamic nucleosome
“We have revealed the existence of two types of promoters, which differ by the presence of ‘fragile’ nucleosomes”, says Slawomir Kubik, first author of the study and researcher at UNIGE. The scientists also found out that the type of promoter containing ‘fragile’ nucleosomes is strongly associated with high levels of transcription. They speculate that the dynamic nature of the ‘fragile’ nucleosome plays an important role in increasing access of the proteins initiating the transcription to the promoter. “The genome probably stays in a very compact state most of the time, with nucleosomes winding the DNA like a tight spring. We believe that the presence of dynamic nucleosomes at highly expressed genes helps to unwind this spring rapidly and as often as necessary”, comments David Shore.