ArticleGenome biology2020
Cis and trans effects differentially contribute to the evolution of promoters and enhancers.
Article in Genome biology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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Who cites it
40 citing papers in PubMed, 73 citations in OpenAlex.
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- Refining the resolution of the yeast genotype-phenotype map using single-cell RNA-sequencing.eLife · 2025Article
- Lipid-lowering drug targets associated with risk of respiratory disease: a Mendelian randomization study.BMC pulmonary medicine · 2025Article
- The emergence and evolution of gene expression in genome regions replete with regulatory motifs.eLife · 2024Article
- Higher order interaction analysis quantifies coordination in the epigenome revealing novel biological relationships in Kabuki syndrome.Briefings in bioinformatics · 2024Article
- Unifying framework explaining how parental regulatory divergence can drive gene expression in hybrids and allopolyploids.Nature communications · 2024Article
- Massively parallel screen uncovers many rare 3' UTR variants regulating mRNA abundance of cancer driver genes.Nature communications · 2024Article
- Transforming our understanding of species-specific gene regulation.Cell genomics · 2024Article
- Human gene regulatory evolution is driven by the divergence of regulatory element function in both cis and trans.Cell genomics · 2024Article
- Super-enhancers: drivers of cells' identities and cells' debacles.Epigenomics · 2024Review
- Dissecting the sequence and structural determinants guiding m6A deposition and evolution via inter- and intra-species hybrids.Genome biology · 2024Article
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Corrections and comments
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Authors and funding
7 authors at 4 institutions in 3 countries.
Funding
Abstract
backgroundGene 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.
resultsOur 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.
conclusionsOur 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.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.