A clustering property of highly-degenerate transcription factor binding sites in the mammalian genome.

A clustering property of highly-degenerate transcription factor binding sites in the mammalian genome.
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DOI:
10.1093/nar/gkl248
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发表时间:
2006
影响因子:
14.9
通讯作者:
Zhang MQ
Zhang MQ
中科院分区:
生物学2区
文献类型:
--
作者:
Zhang C;Xuan Z;Otto S;Hover JR;McCorkle SR;Mandel G;Zhang MQ

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转录因子结合位点(Transcription factor binding sites, TFBSs)是与转录因子相互作用的DNA短序列,调控基因表达。由于这些结合位点的长度相对较短,目前还不清楚蛋白质- dna相互作用的特异性是如何实现的。在这里,我们对转录抑制因子RE1沉默转录因子(REST)以及其他几种具有代表性的哺乳动物tf (c-myc、p53、HNF-1和CREB)的tfbs样序列进行了全基因组分析。我们发现这些tf的不精确位点的非随机分布,称为高度简并的TFBSs,它们在同源结合位点周围富集。通过对人类、小鼠和大鼠同源启动子的比较发现,这些高度退化位点的保守性明显高于预期的随机性,表明它们是在进化过程中被积极选择的。我们认为这种排列为功能靶点选择提供了有利的基因组景观。
Transcription factor binding sites (TFBSs) are short DNA sequences interacting with transcription factors (TFs), which regulate gene expression. Due to the relatively short length of such binding sites, it is largely unclear how the specificity of protein–DNA interaction is achieved. Here, we have performed a genome-wide analysis of TFBS-like sequences for the transcriptional repressor, RE1 Silencing Transcription Factor (REST), as well as for several other representative mammalian TFs (c-myc, p53, HNF-1 and CREB). We find a nonrandom distribution of inexact sites for these TFs, referred to as highly-degenerate TFBSs, that are enriched around the cognate binding sites. Comparisons among human, mouse and rat orthologous promoters reveal that these highly-degenerate sites are conserved significantly more than expected by random chance, suggesting their positive selection during evolution. We propose that this arrangement provides a favorable genomic landscape for functional target site selection.
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发表时间: 2002-01-22
影响因子: 11.1
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