GSE140574 Analysis of regulatory element evolution between human and mouse reveals a lack of cis-trans compensation

Contributors : Kaia Mattioli ; Winona Oliveros ; Chiara Gerhardinger ; Daniel Andergassen ; Philipp G Maass ; John L Rinn ; Marta Mel éSeries Type : Expression profiling by high throughput sequencing ; OtherOrganism : Homo sapiens ; Mus musculus ; synthetic constructGene expression differences between species are driven by both cis and trans effects. Whereas cis effects on gene expression are due to nearby genetic variants, trans effects are due to distal genetic variants that affect diffusible elements such as transcription factors. However, as previous studies have mostly assessed the impacts of cis and trans effects at the gene level, how cis and trans effects differentially impact regulatory elements such as enhancers and promoters remains poorly understood. Here, we used massively parallel reporter assays to directly measure cis and trans effects between human and mouse embryonic stem cells at thousands of individual regulatory elements, including enhancers as well as promoters of both protein-coding and long non-coding RNA genes. Our approach revealed that cis effects are widespread across regulatory elements, and the strongest cis effects are associated with the disruption of motifs recognized by strong transcriptional activators. Conversely, we found that trans effects are rare but stronger in enhancers than promoters, and can be attributed to a subset of transcription factors that are differentially expressed between human and mouse. While previous gene-based ...
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Expression profiling by high throughput sequencing Other Homo sapiens Mus musculus synthetic construct Source Type: research

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