Analysis of the vertebrate insulator protein CTCF-binding sites in the human genome

Analysis of the vertebrate insulator protein CTCF-binding sites in the human genome
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DOI:
10.1016/j.cell.2006.12.048
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发表时间:
2007-03-23
期刊:
影响因子:
64.5
通讯作者:
Ren, Bing
Ren, Bing
中科院分区:
生物学1区
文献类型:
--
作者:
Kim, Tae Hoon;Abdullaev, Ziedulla K.;Ren, Bing

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绝缘元素通过防止异染色质的扩散和限制转录增强子的激活来影响基因表达。在脊椎动物中,绝缘子的功能需要与CCCTC结合因子(CTCF)的关联,该蛋白识别长而多样的核苷酸序列。尽管绝缘子在基因调节中至关重要,但只有少数报道。在这里,我们描述了人类基因组潜在绝缘体中的13,804个CTCF结合位点,这些位点在原代人成纤维细胞中实验发现。这些序列中的大多数远离转录起始位点,它们的分布与基因密切相关。它们中的大多数适合共识基序高度保守,适合预测其他脊椎动物基因组中CTCF驱动的可能的绝缘子。另外,在不同的细胞类型中,CTCF定位在很大程度上是不变的。我们的结果为调查绝缘体功能以及CTCF站点的其他一般和进化保守的活动提供了资源。
Insulator elements affect gene expression by preventing the spread of heterochromatin and restricting transcriptional enhancers from activation of unrelated promoters. In vertebrates, insulator's function requires association with the CCCTC-binding factor (CTCF), a protein that recognizes long and diverse nucleotide sequences. While insulators are critical in gene regulation, only a few have been reported. Here, we describe 13,804 CTCF-binding sites in potential insulators of the human genome, discovered experimentally in primary human fibroblasts. Most of these sequences are located far from the transcriptional start sites, with their distribution strongly correlated with genes. The majority of them fit to a consensus motif highly conserved and suitable for predicting possible insulators driven by CTCF in other vertebrate genomes. In addition, CTCF localization is largely invariant across different cell types. Our results provide a resource for investigating insulator function and possible other general and evolutionarily conserved activities of CTCF sites.