DNase footprint signatures are dictated by factor dynamics and DNA sequence.
DNase footprint signatures are dictated by factor dynamics and DNA sequence.
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DOI：
10.1016/j.molcel.2014.08.016
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发表时间：
2014-10-23
期刊：
影响因子：
16
通讯作者：
Hager, Gordon L.
中科院分区：
文献类型：
--
作者：
Sung, Myong-Hee;Guertin, Michael J.;Baek, Songjoon;Hager, Gordon L.
基因组足迹法已成为一种无偏的发现方法，在同源DNA在体内的转录因子（TF）占用。足迹法的基本前提是序列特异性TF-DNA相互作用与对核酸酶的局部抗性相关，在可接近的染色质内留下可观察到的切割特征。这一现象被解释为意味着保护的关键核苷酸的稳定结合的蛋白质因子。然而，这一模型与以前的报道相冲突，许多TF在活细胞中以秒的时间尺度与特异性结合位点交换。我们发现，具有短的DNA停留时间的TF在结合的基序元素没有足迹。此外，足迹内的核酸酶切割谱源自因子结合位点中的DNA序列，而不是来自占据特定核苷酸的蛋白质。这些发现表明TF足迹的理解，并揭示了使用这种方法全面重建TF调控网络的局限性。
Genomic footprinting has emerged as an unbiased discovery method for transcription factor (TF) occupancy at cognate DNA in vivo. A basic premise of footprinting is that sequence-specific TF-DNA interactions are associated with localized resistance to nucleases, leaving observable signatures of cleavage within accessible chromatin. This phenomenon is interpreted to imply protection of the critical nucleotides by the stably bound protein factor. However, this model conflicts with previous reports of many TFs exchanging with specific binding sites in living cells on a time scale of seconds. We show that TFs with short DNA residence times have no footprints at bound motif elements. Moreover, the nuclease cleavage profile within a footprint originates from the DNA sequence in the factor binding site, rather than from the protein occupying specific nucleotides. These findings suggest a revised understanding of TF footprinting, and reveal limitations in comprehensive reconstruction of the TF regulatory network using this approach.
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影响因子：
64.8
作者：
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通讯作者：
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