染色质重塑与TonEBP依赖的基因转录调控

发布时间：2018-08-17 08:39

【摘要】： 细胞在高渗环境下首先通过细胞外离子迅速内流和细胞内水外流来保证细胞内外的渗透压平衡,此时伴有细胞皱缩等形态改变,这是细胞对高渗应激的即刻反应,但它的代偿保护作用是暂时和有限的,并且细胞内持续的高离子状态对细胞是非常有害的,可以诱发细胞凋亡或死亡。此时细胞会激活另外一个长效代偿机制,那就是通过增加一系列渗透压反应基因的转录翻译,从而增加有机渗透物合成、促进胞外有机渗透物内流或减少有机渗透物降解,最终使有机渗透物在细胞内聚集,从而恢复细胞内外的渗透压平衡,这些有机渗透物对细胞是无害的。目前的研究表明渗透压反应基因的转录合成增加是依赖于特异性转录因子TonEBP与TonE增强子元件的结合而启动的。真核细胞的DNA在细胞核内是以染色质的形式存在的。DNA缠绕组蛋白组成核小体,然后进一步形成染色质,组蛋白对DNA来说既是一个结构上的保护因素又是一个功能上的抑制因素。基因转录作为一个以DNA为模板的酶学过程必然要涉及到局部染色质如何打开以利于转录起始的过程,这就是染色质重塑过程。目前发现的染色质重塑事件主要有两种,一种是组蛋白翻译后共价修饰,另外是一种ATP酶依赖的核小体重塑。TonEBP作为高渗应激信号途径的一个核转录因子,它启动靶基因转录
[Abstract]:In hyperosmotic environment, the first step is to ensure the balance of osmotic pressure between the cells and the cells through the rapid influx of extracellular ions and the outflow of water in the cells. At this time, the cells are accompanied by morphological changes such as shrinkage of the cells, which is the immediate response of the cells to hyperosmotic stress. However, its compensatory protective effect is temporary and limited, and the persistent high ion state in cells is very harmful to cells, which can induce cell apoptosis or death. At this point, the cell activates another long-term compensatory mechanism, that is, by increasing the transcriptional translation of a series of osmotic response genes, thus increasing the synthesis of organic osmosis, promoting the influx of extracellular organic osmosis or reducing the degradation of organic osmosis. Finally, the organic osmosis aggregates in the cell, thus restoring the balance of osmotic pressure inside and outside the cell, these organic osmosis is harmless to the cell. Current studies have shown that the increased transcription synthesis of osmotic pressure response genes is triggered by the binding of specific transcription factor TonEBP to TonE enhancer elements. The DNA of eukaryotic cells in the nucleus is composed of chromatin. DNA-wound histones form nucleosomes and then form chromatin. Histone is not only a structural protective factor but also a functional inhibitory factor for DNA. As an enzymatic process based on DNA template, gene transcription must involve the process of local chromatin opening to facilitate transcription initiation, which is called chromatin remodeling process. There are two main chromatin remodeling events, one is post-covalent modification of histone, and the other is a ATP enzyme-dependent nucleosome remodeling. TonEBP acts as a nuclear transcription factor in hyperosmotic stress signaling pathway, which activates target gene transcription.
【学位授予单位】：重庆医科大学
【学位级别】：博士
【学位授予年份】：2006
【分类号】：R346

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