Structural constraints in collaborative competition of transcription factors against the nucleosome.

Structural constraints in collaborative competition of transcription factors against the nucleosome.
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DOI:
10.1016/j.jmb.2011.07.032
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发表时间:
2011-09-30
影响因子:
5.6
通讯作者:
Widom J
Widom J
中科院分区:
生物学2区
文献类型:
--
作者:
Moyle-Heyrman G;Tims HS;Widom J

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转录因子(TF)结合的协同性在真核生物基因调控中是必不可少的,并通过多种机制产生。在这里,我们关注一种机制,协作竞争,这是一个有趣的机制,因为它既自动产生,不需要TF共同进化,也自发产生,不需要atp依赖性核小体重塑因子。先前的合作竞争实验研究分析了合作tf对的靶位点包含在核小体的同一侧的情况。在这里,我们利用新的测定方法来测量蛋白质结合对核小体DNA靶点的协同性。我们专注于体内相关性最大的情况,其中一个结合位点位于核小体的末端附近,而另一个结合位点位于整个核小体的不同位置。我们的研究结果揭示了核小体同侧成对位点的能量显著的正(有利)协同性,但对于所研究的情况,核小体相反侧位点之间的能量不显著的协同性。这些发现暗示了TF结合位点在基因组中间隔在1 / 2核小体长度(74 bp)以内的特殊意义,并可能被证明对全基因组协同作用TF的预测有用。
Cooperativity in transcription factor (TF) binding is essential in eukaryotic gene regulation, and arises through diverse mechanisms. Here we focus on one mechanism, collaborative competition, which is of interest because it arises both automatically, with no requirement for TF co-evolution, and spontaneously, with no requirement for ATP-dependent nucleosome remodeling factors. Previous experimental studies of collaborative competition analyzed cases in which target sites for pairs of cooperating TFs were contained within the same side of the nucleosome. Here we utilize new assays to measure cooperativity in protein binding to pairs of nucleosomal DNA target sites. We focus on the cases that are of greatest in vivo relevance, in which one binding site is located close to the end of a nucleosome, and the other binding site is located at diverse positions throughout the nucleosome. Our results reveal energetically significant positive (favorable) cooperativity for pairs of sites on the same side of the nucleosome, but, for the cases examined, energetically insignificant cooperativity between sites on opposite sides of the nucleosome. These findings imply a special significance for TF binding sites that are spaced within one half nucleosome length (74 bp) or less along the genome, and may prove useful for prediction of cooperatively acting TFs genome-wide.
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