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CPG METHYLATION REMODELS CHROMATIN STRUCTURE IN VITRO

机译:CPG甲基化可体外重塑染色质结构

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One of the mechanisms proposed to explain how CpG methylation effects gene repression invokes a DNA methylation-determined chromatin structure. Previous work implied that this DNA modification does not influence nucleosome formation in vitro, thus current models propose that certain non-histone proteins or a preferential affinity by linker histones for methylated DNA may mediate changes in chromatin structure. We have reinvestigated whether CpG methylation alters the chromatin structure of reconstitutes comprising only core histones and DNA. We find that DNA methylation prevents the histone octamer from interacting with an otherwise high affinity positioning sequence in the promoter region of the chicken adult beta-globin gene. This exclusion is attributed to methylation-determined changes in DNA structure within a triplet of CpG dinucleotides. In the affected nucleosome, this sequence motif is located 1.5 helical turns from the dyad axis and is oriented towards the histone core. These findings establish that DNA methylation does have the capacity to modulate chromatin structure directly, at its most fundamental level. Furthermore, our observations strongly suggest that a very limited number of nucleotides can make a decisive contribution to the translational positioning of nucleosomes. (C) 1997 Academic Press Limited. [References: 69]
机译:提出的解释机制之一是解释CpG甲基化如何影响基因抑制,从而调用DNA甲基化确定的染色质结构。先前的工作暗示该DNA修饰不会在体外影响核小体的形成,因此当前的模型提出某些非组蛋白或甲基化DNA的连接蛋白对组蛋白的优先亲和力可能介导染色质结构的改变。我们已经重新研究了CpG甲基化是否会改变仅包含核心组蛋白和DNA的重组体的染色质结构。我们发现DNA甲基化阻止了组蛋白八聚体与鸡成年β-珠蛋白基因启动子区域中的其他高亲和力定位序列相互作用。此排除归因于CpG二核苷酸三联体中甲基化确定的DNA结构变化。在受影响的核小体中,该序列基序位于距二倍体轴1.5螺旋匝处,并朝向组蛋白核心。这些发现表明,DNA甲基化确实具有在其最基本的水平上直接调节染色质结构的能力。此外,我们的观察结果强烈表明,数量非常有限的核苷酸可以对核小体的翻译定位起决定性作用。 (C)1997 Academic Press Limited。 [参考:69]

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