Non-targeted transcription factors motifs are a systemic component of ChIP-seq datasets.
Non-targeted transcription factors motifs are a systemic component of ChIP-seq datasets.
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DOI：
10.1186/s13059-014-0412-4
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发表时间：
2014-07-29
期刊：
影响因子：
12.3
通讯作者：
Wasserman WW
中科院分区：
文献类型：
--
作者：
Worsley Hunt R;Wasserman WW
全球注释人类基因组非编码部分的努力在很大程度上依赖于高通量 DNA 测序 (ChIP-seq) 生成的染色质免疫沉淀数据。 ChIP-seq 通常成功地详细描述了免疫沉淀转录因子 (TF) 结合的基因组片段，但几乎所有数据集都包含缺乏 TF 规范基序的基因组区域。这些区域是否与免疫沉淀的 TF 有关，或者尽管使用了对照，是否仍有一部分峰可归因于其他原因，仍有待确定。对针对序列特异性 DNA 结合 TF 生成的数百个 ChIP-seq 数据集进行的分析揭示了一小部分 TF 结合概况，反复观察到预测的 TF 结合位点基序显着富集。该组对相关的结合配置文件进行分组，包括：CTCF 类、ETS 类、JUN 类和 THAP11 类配置文件。这些频繁富集的配置文件被称为“zingers”，以强调它们在不是目标 TF 的数据集中意外富集，以及它们对 TF ChIP-seq 数据解释和分析的潜在影响。据观察，具有 zinger 基序且缺乏 ChIPped TF 基序的峰占 ChIP-seq 数据集的比例高达 45%。不同 TF 数据集之间包含 zinger 基序的区域存在大量重叠，这表明恢复这些区域的机制不是 TF 特有的。基于靠近粘连蛋白结合片段的辛格区域，提出了装载站模型。对 Zingers 的进一步研究将增进对基因调控的理解。本文的在线版本 (doi:10.1186/s13059-014-0412-4) 包含补充材料，可供授权用户使用。
The global effort to annotate the non-coding portion of the human genome relies heavily on chromatin immunoprecipitation data generated with high-throughput DNA sequencing (ChIP-seq). ChIP-seq is generally successful in detailing the segments of the genome bound by the immunoprecipitated transcription factor (TF), however almost all datasets contain genomic regions devoid of the canonical motif for the TF. It remains to be determined if these regions are related to the immunoprecipitated TF or whether, despite the use of controls, there is a portion of peaks that can be attributed to other causes. Analyses across hundreds of ChIP-seq datasets generated for sequence-specific DNA binding TFs reveal a small set of TF binding profiles for which predicted TF binding site motifs are repeatedly observed to be significantly enriched. Grouping related binding profiles, the set includes: CTCF-like, ETS-like, JUN-like, and THAP11 profiles. These frequently enriched profiles are termed ‘zingers’ to highlight their unanticipated enrichment in datasets for which they were not the targeted TF, and their potential impact on the interpretation and analysis of TF ChIP-seq data. Peaks with zinger motifs and lacking the ChIPped TF’s motif are observed to compose up to 45% of a ChIP-seq dataset. There is substantial overlap of zinger motif containing regions between diverse TF datasets, suggesting a mechanism that is not TF-specific for the recovery of these regions. Based on the zinger regions proximity to cohesin-bound segments, a loading station model is proposed. Further study of zingers will advance understanding of gene regulation. The online version of this article (doi:10.1186/s13059-014-0412-4) contains supplementary material, which is available to authorized users.
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影响因子：
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