Genome-wide discovery of active regulatory elements and transcription factor footprints in Caenorhabditis elegans using DNase-seq.
Genome-wide discovery of active regulatory elements and transcription factor footprints in Caenorhabditis elegans using DNase-seq.
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DOI：
10.1101/gr.223735.117
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发表时间：
2017-12
期刊：
影响因子：
7
通讯作者：
Sternberg PW
中科院分区：
文献类型：
--
作者：
Ho MCW;Quintero-Cadena P;Sternberg PW
深度测序大小选择的DNA酶I处理的染色质（DNase-seq）允许高分辨率测量染色质对DNA酶I切割的可及性，允许鉴定从头活性顺式调节模块（CRM）和单个转录因子（TF）结合位点。我们将DNase-seq适应于从C. elegans胚胎和L1逮捕幼虫，以产生高分辨率的TF结合图。超过一半的胚胎DNase I超敏感位点（DHS）被注释为非编码，24%的基因间，12%的启动子，28%的内含子，与L1逮捕幼虫观察到类似的统计数据。非编码DHS是高度保守的，并且富含增强子活性和转录的标记。我们针对来自myo-2、myo-3、hlh-1、elt-2和lin-26/lir-1的已知增强子验证了非编码DHS，并概括了17个已知增强子中的15个。然后，我们挖掘DNase-seq数据，以确定推定的活性CRM和TF足迹。与单独的基序相比，使用DNase-seq数据改善了组织特异性表达的预测。在初步功能测试中，来自pha-4、icl-1和ceh-13的15个DHS中的10个驱动转基因C.优雅总的来说，我们提供了26，644个假定的标准物质在胚胎中含有55，890个TF足迹，以及15，841个假定的标准物质在L1停滞幼虫中含有32，685个TF足迹的实验注释。
Deep sequencing of size-selected DNase I–treated chromatin (DNase-seq) allows high-resolution measurement of chromatin accessibility to DNase I cleavage, permitting identification of de novo active cis-regulatory modules (CRMs) and individual transcription factor (TF) binding sites. We adapted DNase-seq to nuclei isolated from C. elegans embryos and L1 arrest larvae to generate high-resolution maps of TF binding. Over half of embryonic DNase I hypersensitive sites (DHSs) were annotated as noncoding, with 24% in intergenic, 12% in promoters, and 28% in introns, with similar statistics observed in L1 arrest larvae. Noncoding DHSs are highly conserved and enriched in marks of enhancer activity and transcription. We validated noncoding DHSs against known enhancers from myo-2, myo-3, hlh-1, elt-2, and lin-26/lir-1 and recapitulated 15 of 17 known enhancers. We then mined DNase-seq data to identify putative active CRMs and TF footprints. Using DNase-seq data improved predictions of tissue-specific expression compared with motifs alone. In a pilot functional test, 10 of 15 DHSs from pha-4, icl-1, and ceh-13 drove reporter gene expression in transgenic C. elegans. Overall, we provide experimental annotation of 26,644 putative CRMs in the embryo containing 55,890 TF footprints, as well as 15,841 putative CRMs in the L1 arrest larvae containing 32,685 TF footprints.
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影响因子：
2.7
作者：
Fukushige, T;Hawkins, MG;McGhee, JD
通讯作者：
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Sternberg PW
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作者：
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通讯作者：
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