Histones and histone modifications

Histones and histone modifications
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DOI:
10.1016/j.cub.2004.07.007
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发表时间:
2004-07-27
期刊:
影响因子:
9.2
通讯作者:
Laniel, MA
Laniel, MA
中科院分区:
生物学1区
文献类型:
--
作者:
Peterson, CL;Laniel, MA

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想象一下,试着把大约10,000英里长的意大利面条塞进一个篮球里。然后,如果这还不够难的话,试着从这堆乱七八糟的东西中间找到一段独特的一英寸的意大利面,或者试着复制、解开和分离单独的绳子到两端。这个简单的类比说明了一些艰巨的任务与转录,修复和复制的近2米的DNA被包装到一个微小的真核细胞核的范围。这些问题的解决方案都在于将真核生物基因组组装成染色质,染色质是一种结构聚合物,它不仅解决了基本的包装问题,而且还提供了一个动态平台,控制细胞核内所有DNA介导的过程。染色质的基本单位是核小体核心颗粒,它包含147 bp的DNA,包裹在核心组蛋白的八聚体周围近两次。组蛋白八聚体由组蛋白H3和H4的中心异源四聚体组成,两侧是组蛋白H2 A和H2 B的两个异源二聚体。每个核小体由10-60 bp的“接头”DNA分开,并且所得核小体阵列构成直径约10 nm的染色质纤维。这种简单的“串珠”排列被折叠成更浓缩的、约30 nm厚的纤维,这些纤维通过连接体组蛋白与每个核小体核心的结合而稳定(注意,连接体组蛋白在序列上与核心组蛋白不相关)。这样的30 nm纤维然后在体内进一步凝聚以形成100-400 nm厚的界面纤维或更高厚度的界面纤维。
Imagine trying to stuff about 10,000 miles of spaghetti inside a basketball. Then, if that was not difficult enough, attempt to find a unique one inch segment of pasta from the middle of this mess, or try to duplicate, untangle and separate individual strings to opposite ends. This simple analogy illustrates some of the daunting tasks associated with the transcription, repair and replication of the nearly 2 meters of DNA that is packaged into the confines of a tiny eukaryotic nucleus. The solution to each of these problems lies in the assembly of the eukaryotic genome into chromatin, a structural polymer that not only solves the basic packaging problem, but also provides a dynamic platform that controls all DNA-mediated processes within the nucleus.The basic unit of chromatin is the nucleosome core particle, which contains 147 bp of DNA wrapped nearly twice around an octamer of the core histones. The histone octamer is composed of a central heterotetramer of histones H3 and H4, flanked by two heterodimers of histones H2A and H2B. Each nucleosome is separated by 10–60 bp of ‘linker’DNA, and the resulting nucleosomal array constitutes a chromatin fiber of~ 10 nm in diameter. This simple ‘beads-ona-string’arrangement is folded into more condensed,~ 30 nm thick fibers that are stabilized by binding of a linker histone to each nucleosome core (note that linker histones are not related in sequence to the core histones). Such 30 nm fibers are then further condensed in vivo to form 100–400 nm thick interphase fibers or the more highly