Integrative analysis of public ChIP-seq experiments reveals a complex multi-cell regulatory landscape.

Integrative analysis of public ChIP-seq experiments reveals a complex multi-cell regulatory landscape.
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DOI:
10.1093/nar/gku1280
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发表时间:
2015-02-27
影响因子:
14.9
通讯作者:
Ballester B
Ballester B
中科院分区:
生物学2区
文献类型:
--
作者:
Griffon A;Barbier Q;Dalino J;van Helden J;Spicuglia S;Ballester B

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公共数据仓库中迅速积累的大量芯片序列数据为数百个转录因子(TF)提供了全基因组结合位点图。然而,通过整合公共芯片序列数据集并将其与ENCODE TFS图谱相结合,尚未完全了解人类基因组中调控占用空间的程度。为了能够在全基因组范围内识别调控元件,我们收集、分析和保留了395个可用的芯片序列数据集,这些数据集与ENCODE峰合并,总共覆盖237个转录因子。与单独使用ENCODE相比,这个增强的曲目增加了14%的人类基因组调控搜索空间,从而补充和完善了当前的基因组范围占用图,也增加了调控词典的复杂性。作为一个直接的应用,我们使用这个统一的结合谱来注释H3K4me1标记在两个癌细胞系(MCF-7,CRC)中的不同增强子基因座(VEL),并观察到参与癌症发生和增殖的生物关键功能的特定转录因子的丰富。这些转录因子在VEL中的丰富为癌症基因组中检测到的非编码区提供了直接的注释。最后,可与TFS丰富分析工具(http://tagc.univ-mrs.fr/remap/).)一起在线获得该目录的完全访问权限
The large collections of ChIP-seq data rapidly accumulating in public data warehouses provide genome-wide binding site maps for hundreds of transcription factors (TFs). However, the extent of the regulatory occupancy space in the human genome has not yet been fully apprehended by integrating public ChIP-seq data sets and combining it with ENCODE TFs map. To enable genome-wide identification of regulatory elements we have collected, analysed and retained 395 available ChIP-seq data sets merged with ENCODE peaks covering a total of 237 TFs. This enhanced repertoire complements and refines current genome-wide occupancy maps by increasing the human genome regulatory search space by 14% compared to ENCODE alone, and also increases the complexity of the regulatory dictionary. As a direct application we used this unified binding repertoire to annotate variant enhancer loci (VELs) from H3K4me1 mark in two cancer cell lines (MCF-7, CRC) and observed enrichments of specific TFs involved in biological key functions to cancer development and proliferation. Those enrichments of TFs within VELs provide a direct annotation of non-coding regions detected in cancer genomes. Finally, full access to this catalogue is available online together with the TFs enrichment analysis tool (http://tagc.univ-mrs.fr/remap/).
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