生物
染色质免疫沉淀
转录因子
遗传学
芯片排序
DNA结合位点
计算生物学
抑制因子
基因组
芯片对芯片
DNA
染色质
基因
发起人
基因表达
染色质重塑
作者
David S. Johnson,A Mortazavi,R Myers,B Wold
出处
期刊:Science
[American Association for the Advancement of Science (AAAS)]
日期:2007-06-08
卷期号:316 (5830): 1497-1502
被引量:2613
标识
DOI:10.1126/science.1141319
摘要
In vivo protein-DNA interactions connect each transcription factor with its direct targets to form a gene network scaffold. To map these protein-DNA interactions comprehensively across entire mammalian genomes, we developed a large-scale chromatin immunoprecipitation assay (ChIPSeq) based on direct ultrahigh-throughput DNA sequencing. This sequence census method was then used to map in vivo binding of the neuron-restrictive silencer factor (NRSF; also known as REST, for repressor element-1 silencing transcription factor) to 1946 locations in the human genome. The data display sharp resolution of binding position [+/-50 base pairs (bp)], which facilitated our finding motifs and allowed us to identify noncanonical NRSF-binding motifs. These ChIPSeq data also have high sensitivity and specificity [ROC (receiver operator characteristic) area >/= 0.96] and statistical confidence (P <10(-4)), properties that were important for inferring new candidate interactions. These include key transcription factors in the gene network that regulates pancreatic islet cell development.
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