Verschure Pernette J
Swammerdam Institute for Life Sciences, BioCentrum Amsterdam, University of Amsterdam, Kruislaan 318, 1098 SM Amsterdam, The Netherlands.
Biol Cell. 2004 Oct;96(8):569-77. doi: 10.1016/j.biolcel.2004.07.001.
Higher eukaryotic genomes contain both housekeeping genes and genes of which the expression is restricted to a defined time and space. It is well established that a correlation exists between structural organization of the genome and gene expression control. The functional mechanisms underlying this correlation are still poorly understood. Here I describe several observations that are the basis of present concepts of genome organization and nuclear architecture related to functionality. Regarding the relationship between positioning and disturbed cell functionality, I describe observations showing that the proximity of selected gene loci is statistically correlated with their propensity for oncogenic translocations as well as observations of patterns occurring in neurodegenerative disorders where unstable repeats are translated into an expanded polyglutamine tract. Such observations underscore the importance to understand how genetic perturbations lead to the global reorganization of nuclear architecture, chromatin structure and widespread changes in gene expression.
高等真核生物基因组既包含管家基因，也包含那些表达局限于特定时间和空间的基因。基因组的结构组织与基因表达调控之间存在关联，这一点已得到充分证实。然而，这种关联背后的功能机制仍知之甚少。在此，我描述了一些观察结果，这些结果是当前与功能相关的基因组组织和核结构概念的基础。关于定位与细胞功能紊乱之间的关系，我描述了一些观察结果，这些结果表明，选定基因座的邻近性与其发生致癌易位的倾向在统计学上相关，同时也描述了神经退行性疾病中出现的模式，在这些疾病中，不稳定重复序列被翻译成扩展的聚谷氨酰胺序列。这些观察结果强调了理解基因扰动如何导致核结构的全局重组、染色质结构以及基因表达的广泛变化的重要性。
