Weak interaction induces an ON/OFF switch, whereas strong interaction causes gradual change: Folding transition of a long duplex DNA chain by poly-L-lysine
Weak interaction induces an ON/OFF switch, whereas strong interaction causes gradual change: Folding transition of a long duplex DNA chain by poly-L-lysine
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DOI：
10.1021/bm060634j
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发表时间：
2007-01-01
影响因子：
6.2
通讯作者：
Yoshikawa, Kenichi
中科院分区：
文献类型：
--
作者：
Akitaya, Tatsuo;Seno, Asako;Yoshikawa, Kenichi
基因组DNA的大规模构象变化是活细胞中基因激活的基本特征。除了DNA和组蛋白的修饰（如甲基化和乙酰化）之外，序列特异性调控蛋白和DNA之间的键锁相互作用已经被应用于解释该机制。然而，这些机制是否能够解释伴随分化、致癌等的大量基因的ON/OFF开关，目前还不清楚。在本研究中，通过荧光显微镜对DNA分子进行单分子观察，添加了具有不同数量单体单元的聚-L-赖氨酸，（n = 3，5，9和92），我们发现短聚赖氨酸诱导长链双链DNA的高阶结构发生ON/OFF离散转变，而长聚赖氨酸诱导长链双链DNA的高阶结构发生连续渐变。另一方面，具有较低正电荷的聚阳离子诱导DNA压缩的潜力较小。这样一个巨大的DNA之间的构象转变短和大的寡聚体的巨大差异进行了讨论，在一个活细胞中的基因调控机制。
A large-scale conformational change in genomic DNA is an essential feature of gene activation in living cells. Considerable effort has been applied to explain the mechanism in terms of key-lock interaction between sequence-specific regulatory proteins and DNA, in addition to the modification of DNA and histones such as methylation and acetylation. However, it is still unclear whether these mechanisms can explain the ON/OFF switching of a large number of genes that accompanies differentiation, carcinogenesis, etc. In this study, using single-molecule observation of DNA molecules by fluorescence microscopy with the addition of poly-L-lysine with different numbers of monomer units (n = 3, 5, 9, and 92), we found that an ON/OFF discrete transition in the higher-order structure of long duplex DNA is induced by short poly-L-lysine, whereas a continuous gradual change is induced by long poly-L-lysine. On the other hand, polycations with a lower positive charge have less potential to induce DNA compaction. Such a drastic difference in the conformational transition of a giant DNA between short and large oligomers is discussed in relation to the mechanisms of gene regulation in a living cell.