DNA compaction by the nuclear factor-Y

DNA compaction by the nuclear factor-Y
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DOI:
10.1529/biophysj.106.099929
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发表时间:
2007-07-01
影响因子:
3.4
通讯作者:
Finzi, Laura
Finzi, Laura
中科院分区:
生物学3区
文献类型:
--
作者:
Guerra, Rosalinda F.;Imperadori, Laura;Finzi, Laura

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核因子- y (NF-Y)是一种三聚体,具有组蛋白样亚基的ccaat结合转录激活因子,直到最近才被认为是一种典型的启动子转录因子。然而,最近与微阵列方法相关的体内染色质免疫沉淀试验(芯片上的染色质免疫沉淀实验)表明,大部分靶点(40%-50%)位于核心启动子之外。我们将系固粒子运动技术应用于主要组织相容性复合体II类增强子-启动子区域,以表征i),由于NF-Y浓度增加而导致的DNA的渐进压实,II), NF-Y的特定亚基和结构域在该过程中的作用,以及iii), NF-Y与调节因子- x之间的相互作用,这些因子与CCAAT盒子附近的x盒子合作结合。我们的研究表明NF-Y具有组蛋白样活性,因为它可以结合非物种的DNA。具有高亲和力的calally对其进行压实。这种活性取决于所有三聚体亚基及其谷氨酰胺富结构域的存在,似乎被转录辅助因子调节因子- x减弱。最重要的是,nf - y诱导的DNA压缩可能促进启动子-增强子相互作用,这对于表达调控至关重要。
The nuclear factor-Y (NF-Y), a trimeric, CCAAT-binding transcriptional activator with histone-like subunits, was until recently considered a prototypical promoter transcription factor. However, recent in vivo chromatin immunoprecipitation assays associated with microarray methodologies (chromatin immunoprecipitation on chip experiments) have indicated that a large portion of target sites (40%-50%) are located outside of core promoters. We applied the tethered particle motion technique to the major histocompatibility complex class II enhancer-promoter region to characterize i), the progressive compaction of DNA due to increasing concentrations of NF-Y, ii), the role of specific subunits and domains of NF-Y in the process, and iii), the interplay between NF-Y and the regulatory factor-X, which cooperatively binds to the X-box adjacent to the CCAAT box. Our study shows that NF-Y has histone-like activity, since it binds DNA nonspeci. cally with high affinity to compact it. This activity, which depends on the presence of all trimer subunits and of their glutamine-rich domains, seems to be attenuated by the transcriptional cofactor regulatory factor-X. Most importantly NF-Y-induced DNA compaction may facilitate promoter-enhancer interactions, which are known to be critical for expression regulation.