Conservation of transcription factor binding events predicts gene expression across species.-猫眼课题宝

转录因子结合事件的保存预测物种之间的基因表达。

DOI：

10.1093/nar/gkr404

发表时间：

2011-09-01

期刊：

Nucleic acids research

影响因子：

14.9

通讯作者：

中科院分区：

生物学2区

文献类型：

作者：

Hemberg M;Kreiman G

来源链接：

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3167604/?report=classic

最近的技术进步使得确定转录因子（TF）的全基因组结合位点成为可能。跨物种的比较表明，实验定义的TF结合事件（TFBE）的进化保守程度相对较低。使用6种不同的TF在肝细胞和胚胎干细胞从人类和小鼠的结合数据，我们表明，进化保守的TFBE内的orthopathic近端启动子是密切相关的功能，定义为表达的靶基因。我们表明，（i）当靶基因在两个物种中表达时，TFBE的保守程度显着更高;（ii）与单个TF相比，TF组的结合事件保守性增加;（iii）保守的TFBE对靶基因表达的影响大于非保守的TFBE。这些结果将结构元件（TFBE）的保守性与功能（基因表达）的保守性联系起来，并表明比以前的研究所暗示的更高程度的功能保守性。

Recent technological advances have made it possible to determine the genome-wide binding sites of transcription factors (TFs). Comparisons across species have suggested a relatively low degree of evolutionary conservation of experimentally defined TF binding events (TFBEs). Using binding data for six different TFs in hepatocytes and embryonic stem cells from human and mouse, we demonstrate that evolutionary conservation of TFBEs within orthologous proximal promoters is closely linked to function, defined as expression of the target genes. We show that (i) there is a significantly higher degree of conservation of TFBEs when the target gene is expressed in both species; (ii) there is increased conservation of binding events for groups of TFs compared to individual TFs; and (iii) conserved TFBEs have a greater impact on the expression of their target genes than non-conserved ones. These results link conservation of structural elements (TFBEs) to conservation of function (gene expression) and suggest a higher degree of functional conservation than implied by previous studies.