A hydrophilic polymer grafted with a histone tail peptide as an artificial gene regulator
A hydrophilic polymer grafted with a histone tail peptide as an artificial gene regulator
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接枝组蛋白尾肽的亲水性聚合物作为人工基因调节剂
DOI：
10.1016/j.bmc.2011.05.011
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发表时间：
2011
影响因子：
3.5
通讯作者：
Y.
中科院分区：
文献类型：
--
作者：
Shiosaki;S.;Kuramoto;M.;Toita;R.;Mori;T.,Niidome;T.;Katayama;Y.
在染色质中，基因转录通过组蛋白N-末端尾部序列上的翻译后修饰来调节，通常是赖氨酸残基上的乙酰基修饰。为了实现一个简单的染色质基因调控模型，我们设计了一个亲水性聚合物接枝组蛋白H3尾肽。该聚合物与DNA形成的复合物能有效抑制基因表达，但其抑制作用弱于聚赖氨酸与DNA形成的复合物。这种较弱的多聚物通过组蛋白乙酰转移酶使接枝肽的赖氨酸残基乙酰化。随后，由于接枝肽中阳离子电荷减少所带来的复合物的松弛，基因表达被激活。该分子系统是染色质基因调控的第一个功能模型。
In chromatin, gene transcription is regulated through posttranslational modifications on the histoneN-terminal tail sequences, typically an acetyl group modification on lysine residues. To realize a simple model of the gene regulation of chromatin, we designed a hydrophilic polymer grafted with histone H3 tail peptides. The polyplex formed from the polymer and DNA suppressed the gene expression effectively although the polyplex was weaker than the polyplex of poly-l-lysine and DNA. This weaker polyplex afforded the acetylation of the lysine residue of the grafted peptides by histone acetyltransferase. Subsequently, the gene expression was activated due to the relaxation of the polyplex which was brought by a cationic charge decrease in the grafted peptides. This molecular system is the first functional model of the gene regulation of the chromatin.