Role of Nucleic Acid Binding in Sir3p-Dependent Interactions with Chromatin Fibers

Role of Nucleic Acid Binding in Sir3p-Dependent Interactions with Chromatin Fibers
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DOI:
10.1021/bi801705g
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发表时间:
2009-01-20
期刊:
影响因子:
2.9
通讯作者:
Georgel, Philippe T.
Georgel, Philippe T.
中科院分区:
生物学3区
文献类型:
--
作者:
Adkins, Nicholas L.;McBryant, Steve J.;Georgel, Philippe T.

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最近对真核生物基因表达调控机制的研究描绘了一个高度复杂的过程,需要大量分子的协调重排来介导 DNA 可及性。酿酒酵母中的沉默涉及 Sir 蛋白家族。 Sir3p 最初被描述为通过与历史 H3 和 H4 的尾部相互作用来抑制酵母基因组的关键区域,似乎在该过程中具有其他作用,包括参与 DNA 结合成分。我们的体外研究重点是使用结合测定、EM 成像和理论模型来表征 Sir3p-核酸相互作用及其在 Sir3p 介导的沉默中的生物学功能。我们的结果表明,最初的 Sir3p 招募部分是 DNA 驱动的、高度合作的,并且依赖于组蛋白尾部以外的核小体特征。最初的步骤似乎很快就以接头 DNA 作为轨迹传播沉默。
Recent studies of the mechanisms involved in the regulation of gene expression in eukaryotic organisms depict a highly complex process requiring a coordinated rearrangement of numerous molecules to mediate DNA accessibility. Silencing in Saccharomyces cerevisiae involves the Sir family of proteins. Sir3p, originally described as repressing key areas of the yeast genome through interactions with the tails of histories H3 and H4, appears to have additional roles in that process, including involvement with a DNA binding component. Our in vitro studies focused on the characterization of Sir3p-nucleic acid interactions and their biological functions in Sir3p-mediated silencing using binding assays, EM imaging, and theoretical modeling. Our results suggest that the initial Sir3p recruitment is partially DNA-driven, highly cooperative, and dependent on nucleosomal features other than histone tails. The initial step appears to be rapidly followed by the spreading of silencing using linker DNA as a track.