当前位置: X-MOL 学术Genome Biol. › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
Cis and trans effects differentially contribute to the evolution of promoters and enhancers
Genome Biology ( IF 12.3 ) Pub Date : 2020-08-20 , DOI: 10.1186/s13059-020-02110-3
Kaia Mattioli 1, 2 , Winona Oliveros 3 , Chiara Gerhardinger 1 , Daniel Andergassen 1 , Philipp G Maass 4, 5 , John L Rinn 6 , Marta Melé 3
Affiliation  

Gene expression differences between species are driven by both cis and trans effects. Whereas cis effects are caused by genetic variants located on the same DNA molecule as the target gene, trans effects are due to genetic variants that affect diffusible elements. Previous studies have mostly assessed the impact of cis and trans effects at the gene level. However, how cis and trans effects differentially impact regulatory elements such as enhancers and promoters remains poorly understood. Here, we use massively parallel reporter assays to directly measure the transcriptional outputs of thousands of individual regulatory elements in embryonic stem cells and measure cis and trans effects between human and mouse. Our approach reveals that cis effects are widespread across transcribed regulatory elements, and the strongest cis effects are associated with the disruption of motifs recognized by strong transcriptional activators. Conversely, we find that trans effects are rare but stronger in enhancers than promoters and are associated with a subset of transcription factors that are differentially expressed between human and mouse. While we find that cis-trans compensation is common within promoters, we do not see evidence of widespread cis-trans compensation at enhancers. Cis-trans compensation is inversely correlated with enhancer redundancy, suggesting that such compensation may often occur across multiple enhancers. Our results highlight differences in the mode of evolution between promoters and enhancers in complex mammalian genomes and indicate that studying the evolution of individual regulatory elements is pivotal to understand the tempo and mode of gene expression evolution.

中文翻译:

顺式和反式效应对启动子和增强子的进化贡献不同

物种之间的基因表达差异是由顺式和反式效应驱动的。顺式效应是由与靶基因位于同一 DNA 分子上的遗传变异引起的,反式效应是由于影响可扩散元件的遗传变异引起的。以前的研究大多在基因水平上评估了顺式和反式效应的影响。然而,顺式和反式效应如何对增强子和启动子等调控元件产生不同的影响仍然知之甚少。在这里,我们使用大规模并行报告基因检测直接测量胚胎干细胞中数千个单独调节元件的转录输出,并测量人和小鼠之间的顺式和反式效应。我们的方法表明顺式效应在转录调控元件中广泛存在,最强的顺式效应与强转录激活因子识别的基序的破坏有关。相反,我们发现反式效应很少见,但在增强子中比启动子更强,并且与人类和小鼠之间差异表达的转录因子子集相关。虽然我们发现顺反补偿在启动子中很常见,但我们没有看到增强子中普遍存在顺反补偿的证据。顺反补偿与增强子冗余呈负相关,表明这种补偿可能经常发生在多个增强子之间。
更新日期:2020-08-20
down
wechat
bug