Identification of novel functional TBP-binding sites and general factor repertoires
Identification of novel functional TBP-binding sites and general factor repertoires
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DOI：
10.1038/sj.emboj.7601550
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发表时间：
2007-02-21
期刊：
影响因子：
11.4
通讯作者：
Stunnenberg, Hendrik
中科院分区：
文献类型：
--
作者：
Denissov, Sergey;van Driel, Marc;Stunnenberg, Hendrik
我们目前的知识，一般的转录因子的要求，由三种哺乳动物RNA聚合酶是基于少量的模型启动子。在这里，我们提出了一个全面的染色质免疫沉淀（ChIP）芯片上分析28个转录因子的一个大的已知的和新的TATA结合蛋白（TBP）结合位点的实验确定通过ChIP克隆。一个大部分的识别TBP结合位点位于内含子或缺乏基因/mRNA注释，并发现直接转录。ChIP芯片数据和功能研究的综合分析显示，迄今为止被认为是RNA聚合酶II（RNAP II）特异性的TAF 12也参与RNAP I转录。RNAP II启动子位于CpG岛和非CpG岛的一般转录因子和含TAF的复合物的不同配置文件被发现，表明不同的转录起始途径。我们的研究拓宽了一般转录因子功能的范围，并发现了人类基因组中大量新颖的功能性TBP结合位点。
Our current knowledge of the general factor requirement in transcription by the three mammalian RNA polymerases is based on a small number of model promoters. Here, we present a comprehensive chromatin immunoprecipitation (ChIP)-on-chip analysis for 28 transcription factors on a large set of known and novel TATA-binding protein (TBP)-binding sites experimentally identified via ChIP cloning. A large fraction of identified TBP-binding sites is located in introns or lacks a gene/mRNA annotation and is found to direct transcription. Integrated analysis of the ChIP-on-chip data and functional studies revealed that TAF12 hitherto regarded as RNA polymerase II (RNAP II)-specific was found to be also involved in RNAP I transcription. Distinct profiles for general transcription factors and TAF-containing complexes were uncovered for RNAP II promoters located in CpG and non-CpG islands suggesting distinct transcription initiation pathways. Our study broadens the spectrum of general transcription factor function and uncovers a plethora of novel, functional TBP-binding sites in the human genome.