Intrinsic variability of gene expression encoded in nucleosome positioning sequences
Intrinsic variability of gene expression encoded in nucleosome positioning sequences
复制标题
DOI：
10.1038/ng.319
复制
发表时间：
2009-04-01
期刊：
影响因子：
30.8
通讯作者：
Kim, Young-Joon
中科院分区：
文献类型：
--
作者：
Choi, Jung Kyoon;Kim, Young-Joon
基因表达的变异是单细胞（1-3）、个体（4-6）和种群或物种（7-9）之间生物多样性的重要材料。在这里，我们表明，表达变异性是一种内在的属性，持续在这些不同的水平。每个启动子似乎都有一个独特的能力来响应外部信号，这些信号可以是环境的，遗传的甚至是随机的。我们的研究发现，在一个关键的调控区域，大多数转录起始位点和TATA元件的位置，从典型的无核小体状态的偏差，一个共同定位的核小体的nucleosome-responsive启动子的组织。可变启动子的这一区域中的核苷酸序列显示出DNA弯曲的高倾向和特定二核苷酸的周期性分布，编码DNA-核小体相互作用的偏好。在去除该核小体以进行基因激活的过程中可能发生可变表达。这是启动子序列如何内在地编码调节灵活性的一个独特例子，这对于适应、发育和进化等生物过程至关重要。
Variation in gene expression is an essential material for biological diversity among single cells(1-3), individuals(4-6) and populations or species(7-9). Here we show that expression variability is an intrinsic property that persists at those different levels. Each promoter seems to have a unique capacity to respond to external signals that can be environmental, genetic or even stochastic. Our investigation into nucleosome organization of variably responding promoters revealed a commonly positioned nucleosome at a critical regulatory region where most transcription start sites and TATA elements are located, a deviation from typical nucleosome-free status. The nucleotide sequences in this region of variable promoters showed a high propensity for DNA bending and a periodic distribution of particular dinucleotides, encoding preferences for DNA-nucleosome interaction. Variable expression is likely to occur during removal of this nucleosome for gene activation. This is a unique example of how promoter sequences intrinsically encode regulatory flexibility, which is vital for biological processes such as adaptation, development and evolution.