Bivariate Genomic Footprinting Detects Changes in Transcription Factor Activity.

Bivariate Genomic Footprinting Detects Changes in Transcription Factor Activity.
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DOI:
10.1016/j.celrep.2017.05.003
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发表时间:
2017-05-23
期刊:
影响因子:
8.8
通讯作者:
Hager GL
Hager GL
中科院分区:
生物学1区
文献类型:
--
作者:
Baek S;Goldstein I;Hager GL

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转录因子(Transcription Factor,TF)响应激活信号结合DNA并调节基因表达。TF结合可以通过保护结合序列免受DNA酶消化(即足迹)来测量。在这里,我们报告说,80%的TF结合基序没有显示出可测量的足迹,部分原因是由于基序序列内的可变切割模式。为了更忠实地描绘TF对染色质的影响,我们开发了一种算法,该算法捕获了对染色质可及性的两种TF依赖性影响-足迹和基序侧翼可及性。该算法称为双变量基因组足迹(BaGFoot),可有效检测TF活性。BaGFoot对不同的可及性测定(DNase-seq,ATAC-seq),所有检查的峰调用程序以及各种切割偏倚校正方法都具有鲁棒性。BaGFoot可靠地预测TF结合,并提供有关TF的有价值的信息,影响染色质可及性在各种生物系统和以下各种生物事件,包括在绝对足迹不能确定的情况下。
In response to activating signals, transcription factors (TFs) bind DNA and regulate gene expression. TF binding can be measured by protection of the bound sequence from DNase digestion (i.e. footprint). Here, we report that 80% of TF binding motifs do not show a measurable footprint, partly due to a variable cleavage pattern within the motif sequence. To more faithfully portray the effect of TFs on chromatin, we developed an algorithm that captures two TF-dependent effects on chromatin accessibility - footprinting and motif-flanking accessibility. The algorithm, termed Bivariate Genomic Footprinting (BaGFoot), efficiently detects TF activity. BaGFoot is robust to different accessibility assays (DNase-seq, ATAC-seq), all examined peak-calling programs, and to a variety of cut bias correction approaches. BaGFoot reliably predicts TF binding and provides valuable information regarding the TFs affecting chromatin accessibility in various biological systems and following various biological events, including in cases where an absolute footprint cannot be determined.
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发表时间: 2011-04-01
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影响因子: --
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