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
中科院分区:
文献类型:
--
作者:
Moyle-Heyrman G;Tims HS;Widom J
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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