Binding sites for metabolic disease related transcription factors inferred at base pair resolution by chromatin immunoprecipitation and genomic microarrays
Binding sites for metabolic disease related transcription factors inferred at base pair resolution by chromatin immunoprecipitation and genomic microarrays
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DOI：
10.1093/hmg/ddi378
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发表时间：
2005-11-15
影响因子：
3.5
通讯作者：
Wadelius, C
中科院分区：
文献类型：
--
作者：
Rada-Iglesias, A;Wallerman, O;Wadelius, C
我们提出了一个详细的在体内表征肝细胞转录调控HepG 2细胞，使用染色质免疫沉淀和检测PCR片段为基础的基因组平铺路径阵列覆盖百科全书的DNA元件（ENCODE）地区。我们的数据表明，HNF-4 α和HNF-3 β，这是通常结合到远端调控元件，可能会合作的大部分肝脏转录组的调节，HNF-4 α和USF 1都可以促进H3乙酰化到他们的许多目标。重要的是，对每个转录因子（TF）结合的序列的生物信息学分析显示与体外建立的共有序列高度相似的基序的过度表达。在这些数据的基础上，我们推断出在碱基对分辨率暂定结合位点。其中一些位点先前已通过体外分析发现，一些位点在本研究中已在体外验证。我们的数据表明，类似的方法可用于所有预测/未表征的TF的体内表征，并且该分析可扩展到整个基因组。
We present a detailed in vivo characterization of hepatocyte transcriptional regulation in HepG2 cells, using chromatin immunoprecipitation and detection on PCR fragment-based genomic tiling path arrays covering the encyclopedia of DNA element (ENCODE) regions. Our data suggest that HNF-4 alpha and HNF-3 beta, which were commonly bound to distal regulatory elements, may cooperate in the regulation of a large fraction of the liver transcriptome and that both HNF-4 alpha and USF1 may promote H3 acetylation to many of their targets. Importantly, bioinformatic analysis of the sequences bound by each transcription factor (TF) shows an over-representation of motifs highly similar to the in vitro established consensus sequences. On the basis of these data, we have inferred tentative binding sites at base pair resolution. Some of these sites have been previously found by in vitro analysis and some were verified in vitro in this study. Our data suggests that a similar approach could be used for the in vivo characterization of all predicted/uncharacterized TF and that the analysis could be scaled to the whole genome.