Global analysis of in vivo Foxa2-binding sites in mouse adult liver using massively parallel sequencing.
Global analysis of in vivo Foxa2-binding sites in mouse adult liver using massively parallel sequencing.
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使用大量平行测序对小鼠成年肝脏中体内FOXA2结合位点进行全球分析。
DOI：
10.1093/nar/gkn382
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发表时间：
2008-08
影响因子：
14.9
通讯作者：
Hoodless, Pamela A.
中科院分区：
文献类型：
--
作者：
Wederell, Elizabeth D.;Bilenky, Mikhail;Cullum, Rebecca;Thiessen, Nina;Dagpinar, Melis;Delaney, Allen;Varhol, Richard;Zhao, YongJun;Zeng, Thomas;Bernier, Bridget;Ingham, Matthew;Hirst, Martin;Robertson, Gordon;Marra, Marco A.;Jones, Steven;Hoodless, Pamela A.
Foxa2 (HNF3β) 是对小鼠肝脏的发育和功能至关重要的三个密切相关的转录因子之一。我们使用染色质免疫沉淀和大规模并行 Illumina 1G 测序 (ChIP–Seq) 来创建成人肝脏体内 Foxa2 结合位点的全基因组图谱。超过 65% 的~11.5 k 基因组位点与 Foxa2 结合相关，映射到注释基因的扩展基因区域，而超过 30% 的基因内位点位于第一个内含子内。所有位点中的 20.5% 距离任何注释基因都超过 50 kb，表明与新基因区域相关。 QPCR 分析表明 Foxa2 结合位点的峰高和折叠富集度之间存在很强的正相关性。我们通过将 Foxa2 结合位点与 SAGE 转录组图谱重叠来测量 Foxa2 和肝脏基因表达之间的关系，发现肝脏中表达的 43.5% 的基因也与 Foxa2 结合相关。我们还鉴定了潜在的 Foxa2 相互作用转录因子，其基序在 Foxa2 结合位点附近富集。我们对小鼠肝脏体内 Foxa2 结合位点的综合结果将有助于解决对成人肝功能重要的转录调控网络。
Foxa2 (HNF3β) is a one of three, closely related transcription factors that are critical to the development and function of the mouse liver. We have used chromatin immunoprecipitation and massively parallel Illumina 1G sequencing (ChIP–Seq) to create a genome-wide profile of in vivo Foxa2-binding sites in the adult liver. More than 65% of the ∼11.5 k genomic sites associated with Foxa2 binding, mapped to extended gene regions of annotated genes, while more than 30% of intragenic sites were located within first introns. 20.5% of all sites were further than 50 kb from any annotated gene, suggesting an association with novel gene regions. QPCR analysis demonstrated a strong positive correlation between peak height and fold enrichment for Foxa2-binding sites. We measured the relationship between Foxa2 and liver gene expression by overlapping Foxa2-binding sites with a SAGE transcriptome profile, and found that 43.5% of genes expressed in the liver were also associated with Foxa2 binding. We also identified potential Foxa2-interacting transcription factors whose motifs were enriched near Foxa2-binding sites. Our comprehensive results for in vivo Foxa2-binding sites in the mouse liver will contribute to resolving transcriptional regulatory networks that are important for adult liver function.
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影响因子：
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通讯作者：
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