Human SWI/SNF drives sequence-directed repositioning of nucleosomes on C-myc promoter DNA minicircles.
Human SWI/SNF drives sequence-directed repositioning of nucleosomes on C-myc promoter DNA minicircles.
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人类 SWI/SNF 驱动 C-myc 启动子 DNA 小环上核小体的序列定向重新定位。
DOI：
10.1021/bi7008823
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发表时间：
2007
期刊：
影响因子：
2.9
通讯作者：
Schnitzler,GavinR
中科院分区：
文献类型：
--
作者：
Sims,HillelI;Lane,JacquelineM;Ulyanova,NataliaP;Schnitzler,GavinR
人SWI/SNF(hSWI/SNF)依赖于ATP的染色质重塑复合体是一种肿瘤抑制因子和重要的转录辅助调节因子。SWI/SNF复合体已被证明可以改变核小体的位置，这种活性可能对它们的功能很重要。然而，以前的研究在很大程度上无法确定DNA序列可能在多大程度上控制SWI/SNF复合体的核小体定位。在这里，我们使用微环重塑的方法来提供第一个证据，证明hSWI/SNF以一种序列依赖的方式移动核小体，远离核小体组装过程中喜欢的核小体定位序列。这种重新定位不受DNA缺口的存在的影响，并且可以在没有拓扑异构酶的情况下发生在闭合环状DNA上。我们观察到由人SWI/SNF调节的c-myc启动子产生的微环上有定向的核小体运动，这可能是先前观察到的c-myc激活过程中两个启动子核小体“破坏”的原因之一。我们的结果提出了一个模型，在该模型中，hSWI/SNF引导的核小体离开默认定位序列会导致序列特异性的调控效应。
The human SWI/SNF (hSWI/SNF) ATP-dependent chromatin remodeling complex is a tumor suppressor and essential transcriptional coregulator. SWI/SNF complexes have been shown to alter nucleosome positions, and this activity is likely to be important for their functions. However, previous studies have largely been unable to determine the extent to which DNA sequence might control nucleosome repositioning by SWI/SNF complexes. Here, we employ a minicircle remodeling approach to provide the first evidence that hSWI/SNF moves nucleosomes in a sequence dependent manner, away from nucleosome positioning sequences favored during nucleosome assembly. This repositioning is unaffected by the presence of DNA nicks, and can occur on closed-circular DNAs in the absence of topoisomerases. We observed directed nucleosome movement on minicircles derived from the human SWI/SNF-regulated c-myc promoter, which may contribute to the previously observed “disruption” of two promoter nucleosomes during c-myc activation in vivo. Our results suggest a model wherein hSWI/SNF-directed nucleosome movement away from default positioning sequences results in sequence-specific regulatory effects.