An integrative genomics approach identifies Hypoxia Inducible Factor-1 (HIF-1)-target genes that form the core response to hypoxia.
An integrative genomics approach identifies Hypoxia Inducible Factor-1 (HIF-1)-target genes that form the core response to hypoxia.
复制标题
DOI：
10.1093/nar/gkp425
复制
发表时间：
2009-08
影响因子：
14.9
通讯作者：
Xavier RJ
中科院分区：
文献类型：
--
作者：
Benita Y;Kikuchi H;Smith AD;Zhang MQ;Chung DC;Xavier RJ
转录因子缺氧诱导因子1 （HIF-1）在对氧通量的转录反应中起核心作用。为了深入了解HIF-1调控的分子通路，有必要确定下游靶基因。我们在此报告了一种基于结合计算策略和实验验证的综合基因组方法来识别hif -1靶基因的策略。为了鉴定hif -1靶基因，使用微阵列数据集根据基因对缺氧的差异反应对其进行排序。然后分析这些基因的近端启动子是否存在保守的hif -1结合位点。根据基因对缺氧的反应和hif结合位点评分对基因进行评分和排序。使用这种策略，我们在微阵列中恢复了先前确认的对缺氧有反应的HIF-1靶基因的41%，并提供了预测的HIF-1靶基因目录。我们提出实验验证ANKRD37作为一个新的hif -1靶基因。总之，这些分析表明了在微阵列数据集的背景下恢复新的hif -1靶基因和发现哺乳动物调控元件的潜力。
The transcription factor Hypoxia-inducible factor 1 (HIF-1) plays a central role in the transcriptional response to oxygen flux. To gain insight into the molecular pathways regulated by HIF-1, it is essential to identify the downstream-target genes. We report here a strategy to identify HIF-1-target genes based on an integrative genomic approach combining computational strategies and experimental validation. To identify HIF-1-target genes microarrays data sets were used to rank genes based on their differential response to hypoxia. The proximal promoters of these genes were then analyzed for the presence of conserved HIF-1-binding sites. Genes were scored and ranked based on their response to hypoxia and their HIF-binding site score. Using this strategy we recovered 41% of the previously confirmed HIF-1-target genes that responded to hypoxia in the microarrays and provide a catalogue of predicted HIF-1 targets. We present experimental validation for ANKRD37 as a novel HIF-1-target gene. Together these analyses demonstrate the potential to recover novel HIF-1-target genes and the discovery of mammalian-regulatory elements operative in the context of microarray data sets.
登录
查看更多内容
影响因子：
3.5
作者：
Choi, JH;Park, MJ;Cheong, J
通讯作者：
Cheong, J
DOI：
10.1073/pnas.0407365101
发表时间：
2004-11-16
影响因子：
11.1
作者：
Das, D;Banerjee, N;Zhang, MQ
通讯作者：
Zhang, MQ
影响因子：
4.8
作者：
Cockman, ME;Masson, N;Maxwell, PH
通讯作者：
Maxwell, PH
使用软件套件基因研究阐明转录控制和顺式调节代码。
影响因子：
12.3
作者：
通讯作者：
--
DOI：
10.1111/j.2517-6161.1995.tb02031.x
发表时间：
1995-01-01
影响因子：
5.8
作者：
BENJAMINI, Y;HOCHBERG, Y
通讯作者：
HOCHBERG, Y